bluuebunny/crossref_metadata_2025_split huggingface dataset:
New developments in neurofibromatosis type 2 and vestibular schwannoma
Authors: Ren Yin , Chari Divya A , Vasilijic Sasa , Welling D Bradley , Stankovic Konstantina M 
Published: November 2020

Abstract
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of multiple nervous system tumors due to mutation in the NF2 tumor suppressor gene. The hallmark feature of the NF2 syndrome is the development of bilateral vestibular schwannomas (VS). Although there is nearly 100% penetrance by 60 years of age, some patients suffer from a severe form of the disease and develop multiple tumors at an early age, while others are asymptomatic until later in life. Management options for VS include surgery, stereotactic radiation, and observation with serial imaging; however, currently, there are no FDA-approved pharmacotherapies for NF2 or VS. Recent advancements in the molecular biology underlying NF2 have led to a better understanding of the etiology and pathogenesis of VS. These novel signaling pathways may be used to identify targeted therapies for these tumors. This review discusses the clinical features and treatment options for sporadic- and NF2-associated VS, the diagnostic and screening criteria, completed and ongoing clinical trials, quality of life metrics, and opportunities for future research.
Extreme heat and paediatric emergency department visits in Southwestern Ontario
Authors: Wilk Piotr , Gunz Anna , Maltby Alana , Ravichakaravarthy Tharsha , Clemens Kristin K , Lavigne Éric , Lim Rodrick , Vicedo-Cabrera Ana Maria 
Published: November 2020

Abstract

Objective
The risk of adverse health events is expected to increase with hotter temperatures, particularly among the most vulnerable groups such as elderly persons and children. The objective of this study was to assess the association between extreme heat and daily emergency department visits among children (0 to 17 years) in Southwestern Ontario.

Methods
We examined the average maximum temperature, relative humidity, and daily paediatric emergency department visits in June through August of 2002 to 2019. We reviewed emergency department visits from two academic hospitals. Daily meteorological data from the local weather station were obtained from Environment and Climate Change Canada.

Results
Extreme heat, defined as the 99th percentile of the maximum temperature distribution, occurred at 33.1°C and was associated with an overall 22% increase in emergency department visits, compared to the reference temperature of 21°C. This association was mostly found between the second and fifth day after the exposure, suggesting a slightly delayed effect. The results of the sub-group analysis indicate that the risk of an emergency department visit due to infectious disease increases by 35% and the most pronounced association was noted in children aged 1 to 12 years.

Conclusions
Extreme heat is associated with an increased incidence of emergency department visits in children. As temperatures continue to increase, strategies to mitigate heat-related health risks among children should be developed.
Fiscal Rules as Bargaining Chips
Authors: Piguillem Facundo , Riboni Alessandro 
Published: November 2020

Abstract
Most fiscal rules can be overridden by consensus. We show that this does not make them ineffectual. Since fiscal rules determine the outside option in case of disagreement, the opposition uses them as “bargaining chips” to obtain spending concessions. We show that under some conditions this political bargain mitigates the debt-accumulation problem. We analyse various rules and find that when political polarization is high, harsh fiscal rules (e.g. government shutdown) maximize the opposition’s bargaining power and lead to lower debt accumulation. When polarization is low, less strict fiscal limits (e.g. balanced-budget rule) are preferable. Moreover, we find that the optimal fiscal rules could arise in equilibrium by negotiation. Finally, by insuring against power fluctuations, negotiable rules yield higher welfare than hard ones.
Elevated serum gasdermin D N-terminal implicates monocyte and macrophage pyroptosis in adult-onset Still's disease
Authors: Nagai Hideto , Kirino Yohei , Nakano Hiroto , Kunishita Yosuke , Henmi Riko , Szymanski Ann Marie , Yoshimi Ryusuke , Ombrello Michael J , Nakajima Hideaki 
Published: November 2020

Abstract

Objectives
Elevation of serum IL-18 in adult-onset Still's disease (AOSD) and systemic JIA (sJIA) suggests the role of the inflammasome in these diseases. Gasdermin D is a pore-forming protein playing central roles in inflammasome-mediated inflammation, but its role in rheumatic disease is unknown. We aimed to elucidate the auto-inflammatory mechanisms in AOSD and sJIA.

Methods
Patients with AOSD, sJIA, hemophagocytic lymphohistiocytosis (HLH) and Behçet's disease followed at Yokohama City University (YCU), or US National Institutes of Health (NIH) were included in the study. Disease activity was evaluated by the modified Pouchot score. Ferritin and N-terminal gasdermin D levels in serum and culture supernatant were measured by ELISA. Primary monocytes (Mo) were stimulated with GM-CSF or M-CSF and differentiated into M1 macrophages (Mφ) or M2Mφ, respectively. The number of Mo/Mφ and their viability were monitored over time.

Results
Patients with active AOSD and sJIA had increased levels of serum gasdermin D N-terminal, which correlated with serum ferritin and IL-18 levels. Mo-derived Mφ from active AOSD patients showed reduced cell viability and increased cell death. The number of cultured Mφ cells on day nine was negatively correlated with the serum ferritin and gasdermin D levels. Higher ferritin and gasdermin D levels were observed in the M1Mφ culture supernatant of active AOSD patients. Gasdermin D inhibitors reduced the pyroptosis-mediated ferritin release in Mo.

Conclusion
Elevation of serum gasdermin D N-terminal provides evidence for inflammasome activation triggering gasdermin D-mediated Mo and Mφ pyroptosis in AOSD and possibly sJIA.
Reduced Parasympathetic Activity in Patients With Different Types of Congenital Heart Disease and Associations to Exercise Capacity
Authors: Fritz Celina , Hock Julia , Oberhoffer Renate , Hager Alfred , Ewert Peter , Müller Jan 
Published: November 2020

Purpose:
Current research indicates an imbalance in the autonomic nervous system (ANS) pathway activities in patients with congenital heart disease (CHD). The heart rate variability (HRV) is a measure to quantify activities of the parasympathetic and sympathetic branches. This study evaluated the parasympathetic activity by means of HRV in patients with CHD, regarding diagnostic subgroups and CHD severity, and the association to exercise capacity.

Methods:
From July 2016 to August 2018, a total of 222 patients with different types of CHD (28.4 ± 10.1 yr; 44% female) received breathing-controlled HRV measurement in the supine position. Based on 130 adjacent heartbeats, the root mean square of successive differences (RMSSD), a parasympathetic activity surrogate was estimated and log-transformed. Additionally, all patients underwent a cardiopulmonary exercise test. For comparison, a control group (CG) of 57 (29.0 ± 7.1 yr; 61% female) healthy volunteers was recruited.

Results:
Patients with CHD exhibited reduced parasympathetic activity in comparison to the CG (lnRMSSD CHD: 3.55 ± 0.57 ms vs CG: 3.93 ± 0.55 ms; P < .001), with the lowest parasympathetic activity in patients with Fontan circulation (3.07 ± 0.54 ms; P < .001). Complex CHD (3.40 ± 0.54 ms) had worse values compared with patients with simple (3.87 ± 0.55 ms; P < .001) and moderate severity (3.74 ± 0.54 ms; P < .001). Better parasympathetic activity in CHD patients was associated with increased exercise capacity (r = 0.322; P < .001).

Conclusions:
Impaired parasympathetic activity suggests limited function of the ANS in patients with CHD. Further studies should focus on the association of exercise capacity and ANS to possibly improve parasympathetic activity and functional outcomes.
Daily Step Counts in Participants With and Without Peripheral Artery Disease
Authors: Gardner Andrew W. , Montgomery Polly S. , Wang Ming , Shen Biyi , Casanegra Ana I. , Silva-Palacios Federico , Zhang Shangming , Pomilla William A. , Esponda Omar L. , Kuroki Marcos 
Published: November 2020

Purpose:
We compared the prevalence of participants with and without symptomatic peripheral artery disease (PAD) who met the goals of attaining >7000 and 10 000 steps/d, and we determined whether PAD status was significantly associated with meeting the daily step count goals before and after adjusting for demographic variables, comorbid conditions, and cardiovascular risk factors.

Methods:
Participants with PAD (n = 396) and without PAD (n = 396) were assessed on their walking for 7 consecutive days with a step activity monitor.

Results:
The PAD group took significantly fewer steps/d than the non-PAD control group (6722 ± 3393 vs. 9475 ± 4110 steps/d; P < .001). Only 37.6% and 15.7% of the PAD group attained the goals of walking >7000 and 10 000 steps/d, respectively, whereas 67.9% and 37.4% of the control group attained these goals (P < .001 for each goal). Having PAD was associated with a 62% lower chance of attaining 7000 steps/d than compared with the control group (OR = 0.383; 95% CI, 0.259-0.565; P < .001), and a 55% lower chance of attaining 10 000 steps/d (OR = 0.449; 95% CI, 0.282-0.709; P < .001). Significant covariates (P < .01) included age, current smoking, diabetes, and body mass index.

Conclusions:
Participants with symptomatic PAD had a 29% lower daily step count compared with age- and sex-matched controls, and were less likely to attain the 7000 and 10 000 steps/d goals. Additionally, participants who were least likely to meet the 7000 and 10 000 daily step count recommendations included those who were older, currently smoked, had diabetes, and had higher body mass index.
Seroprevalence of SARS-CoV-2 IgG in healthcare workers and other staff at North Bristol NHS Trust: a sociodemographic analysis
Authors: Jones Christopher R. , Hamilton Fergus W. , Thompson Ameeka , Morris Tim T. , Moran Ed 
Published: November 2020

Structured summaryBackgroundHealthcare workers (HCWs) are at increased risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are limited data exploring the relative impact of geographical and socioeconomic factors on risk of SARS-CoV-2 infection among HCWs.AimTo estimate and explore SARS-CoV-2 IgG antibody seroprevalence in HCWs and support staff at a hospital in South West England.MethodsWe conducted a nested cross-sectional study from May-July 2020. Inverse probability weighted regression was used to estimate seroprevalence of SARS-CoV-2 and associations with demographic and socioeconomic risk factors that were robust to selection into testing.FindingsAttendance for testing varied by demographic and socioeconomic factors. The overall rate of SARS-CoV-2 IgG seroprevalence among tested staff was 9.3% (638/6858). The highest seroprevalence was found in wards associated with SARS-CoV-2 outbreaks and among junior staff with patient-facing roles. Black, Asian and Minority Ethnic (BAME) staff had increased odds of SARS-CoV-2 seroprevalence (adjusted OR: 1.99, 95%CI: 1.69, 2.34; p<0.001) relative to White staff, except for those categorised as Medical/Dental. We found a significant association between neighbourhood deprivation and seroprevalence (p<0.01). Seroprevalence ranged from 12% in staff residing in areas with the greatest relative deprivation to 8.4% in the least deprived.ConclusionTransmission between staff groups is evident within the healthcare setting. BAME individuals were at increased risk of infection with SARS-CoV-2. Work role, area of residence, and neighbourhood deprivation all contribute to SARS-CoV-2 infection risk. As hospitals introduce routine staff SARS-CoV-2 testing they should consider differential uptake of testing among staff groups.
A Microbial Signature Following Bariatric Surgery is Robustly Consistent Across Multiple Cohorts
Authors: Fouladi Farnaz , Carroll Ian M. , Sharpton Thomas J. , Bulik-Sullivan Emily , Heinberg Leslie , Steffen Kristine , Fodor Anthony A. 
Published: November 2020

AbstractBackgroundBariatric surgery induces significant shifts in the gut microbiota which could potentially contribute to weight loss and metabolic benefits. The aim of this study was to characterize a microbial signature following Roux-en-Y Gastric bypass (RYGB) surgery using novel and existing gut microbiota sequence data.ResultsWe generated 16S rRNA gene and metagenomic sequences from fecal samples from patients undergoing RYGB surgery (n = 61 for 16S rRNA gene and n = 135 for metagenomics). We compared these data with three smaller publicly available 16S rRNA gene and one metagenomic datasets from patients who also underwent RYGB surgery. Mixed linear models and machine learning approaches were used to examine the presence of a common microbial signature across studies. Comparison of our new sequences with previous longitudinal studies revealed strikingly similar profiles in both fecal microbiota composition (r = 0.41 ± 0.10; p < 0.05) and metabolic pathways (r = 0.70 ± 0.05; p < 0.001) early after surgery across multiple datasets. Machine learning approaches revealed that the replicable gut microbiota signature associated with RYGB surgery could be used to discriminate pre- and post-surgical samples. Opportunistic pathogen abundance also increased post-surgery in a consistent manner across cohorts.ConclusionOur study reveals a robust microbial signature involving many commensal and pathogenic taxa and metabolic pathways early after RYGB surgery across different studies and sites. Characterization of the effects of this robust microbial signature on outcomes of bariatric surgery could provide insights into the development of microbiome-based interventions for predicting or improving outcomes following surgery.Trial Registrationclinicaltrials.gov, numberNCT03065426. Registered 27 February 2017,https://www.clinicaltrials.gov/ct2/show/NCT03065426
Knowledge and perceptions of COVID-19 among government employees in Ethiopia
Authors: Deressa Wakgari , Worku Alemayehu , Amogne Wondwosson , Getachew Sefonias , Kifle Awgichew , Abebe Workeabeba 
Published: November 2020

AbstractBackgroundIn the absence of effective treatments or vaccines, the spread of the novel coronavirus disease 2019 (COVID-19) pandemic can be minimized by effectively implementing preventive measures. Knowledge and perceptions of the public about COVID-19 play a critical role in behavioral changes. This study aimed to assess the knowledge and perceptions of COVID-19 as well as source of information about the disease among government employees.MethodsA cross-sectional survey of 1,573 government employees from 46 public institutions located in Addis Ababa was undertaken from 8th to 19th June 2020. Paper-based self-administered questionnaires were used for data collection. ANOVA test and t-test were used to assess the difference between groups.ResultsThe respondents demonstrated very high knowledge of the cause of COVID-19 (93%), its main clinical symptoms (>90%), the main modes of transmission (89%), the main preventive measures (>90%). Almost all respondents reported that people with recent travel history (86.8%) or people who had contact with COVID-19 patients (93.5%) were the high-risk groups to be infected with coronavirus. In addition, more than half (50.9%) of the study participants reported that people without travel history nor had contact with confirmed cases are also most likely to be infected with the virus. About 84% of the respondents perceived that older adults and elderly were most at risk to die from COVID-19. Similarly, the majority of the respondents reported that adults with other underlying health problems (95.4%), cigarette smokers (88.1%) and substance users (87.5%) were more likely to die from the disease. An electronic media such as television (85.5%), social media (74.1%), online materials (71.1%) and radio (60.8%) constituted the primary sources of information about COVID-19, followed by healthcare workers (66.6%) and print materials (35.4%). Television (32.2%) and health workers (30.5%) constituted the most trusted sources of information related to COVID-19.ConclusionsThis study has showed higher level of knowledge and favorable perception among respondents about COVID-19. Knowledge and perceptions have great roles in behavioral change and efforts should be focused on improving the perceived susceptibility, severity, and benefits of preventive behavioral changes by providing timely and adequate information.
Lateral habenula mediates defensive responses only when threat and safety memories are in conflict
Authors: Velazquez-Hernandez Geronimo , Sotres-Bayon Francisco 
Published: November 2020

SummarySurvival depends on the ability to adaptively react or execute actions based on previous aversive salient experiences. Although lateral habenula (LHb) activity has been broadly implicated in the regulation of aversively motivated responses, it is not clear under which conditions this brain structure is necessary to regulate defensive responses to a threat. To address this issue, we combined pharmacological inactivations with behavioral tasks that involve aversive and appetitive events and evaluated defensive responses in rats. We found that LHb pharmacological inactivation did not affect cued threat and extinction learning and memory, anxiety-like or reward-seeking behaviors. Surprisingly, we found that LHb inactivation abolished reactive defensive responses (tone-elicited freezing) only when threat (conditioning) and safety memories (extinction and latent inhibition) compete. Consistently, we found that LHb inactivation impaired active defensive responses (platform-mediated avoidance), thereby biasing choice behavior (between avoiding a threat or approaching food) towards reward-seeking responses. Together, our findings suggest that LHb activity mediates defensive responses only when guided by competing threat and safety memories, consequently revealing a previously uncharacterized role for LHb in experience-dependent emotional conflict.
Developing services for long Covid: lessons from a study of wounded healers
Authors: Ladds Emma , Rushforth Alex , Wieringa Sietse , Taylor Sharon , Rayner Clare , Husain Laiba , Greenhalgh Trisha 
Published: November 2020

AbstractPersistent symptoms lasting longer than 3 weeks are thought to affect 10-20% of patients following Covid 19 infection. No formal guidelines exist in the United Kingdom for treating ‘long Covid’ patients and services are sporadic and variable, although additional funding is promised for their development.In this study narrative interviews and focus groups are used to explore the lived experience of 43 healthcare professionals with long Covid. These individuals see the healthcare system from both professional and patient perspectives thus represent an important wealth of expertise to inform service design.We present a set of co-designed quality standards highlighting equity and ease of access, minimal patient care burden, clinical responsibility, a multidisciplinary and evidence-based approach, and patient involvement and apply these to propose a potential care pathway model that could be adapted and translated to improve care of long Covid patients.Summary boxWhat is known?▪Persistent symptoms (“long Covid”) occur after Covid-19 in 10-20% of sufferers▪Services to manage and rehabilitate patients with long Covid are not yet optimal▪UK healthcare workers experience at least a threefold greater risk of Covid-19 infection and face significant occupational exposure▪Healthcare workers with long Covid can offer important insights into service design and developmentWhat is the question?▪What are the experiences of healthcare workers with long Covid and what are the implications from these for service development?What was found▪Healthcare workers experienced a confusing novel condition that imposed high levels of uncertainty and a significant personal and professional impact.▪Using professional contacts, patient- and professional Mindlines, support groups and Communities of Practice all helped to minimize this uncertainty and high quality therapeutic relationships were essential to cope with it.▪Many experienced a lack of compassion during interactions with the healthcare system and were frustrated by challenges accessing, or absence of, appropriate services.▪Suggestions for improvement included an integrated, multi-disciplinary assessment and rehabilitation service; a set of clinical quality standards; and co-created research and service development.What is the implication for practice now?▪This study supports and extends the principles outlined in recently-developed NHS long Covid quality standards and will inform and support design of dedicated long Covid services.
Computational characteristics of interictal EEG as objective markers of epileptic spasms
Authors: Smith Rachel J. , Hu Derek K. , Shrey Daniel W. , Rajaraman Rajsekar , Hussain Shaun A. , Lopour Beth A. 
Published: November 2020

AbstractObjectiveFavorable neurodevelopmental outcomes in epileptic spasms (ES) are tied to early diagnosis and prompt treatment, but uncertainty in the identification of the disease can delay this process. Therefore, we investigated five computational electroencephalographic (EEG) measures as markers of ES.MethodsWe measured 1) amplitude, 2) power spectra, 3) entropy, 4) long-range temporal correlations, via detrended fluctuation analysis (DFA) and 5) functional connectivity of EEG data from ES patients (n=40 patients) and healthy controls (n=20 subjects), with multiple blinded measurements during wakefulness and sleep for each patient.ResultsIn ES patients, EEG amplitude was significantly higher in all electrodes. Shannon and permutation entropy were lower in ES patients than control subjects, while DFA intercept values in ES patients were significantly higher than control subjects. DFA exponent values were not significantly different between the groups. EEG functional connectivity networks in ES patients were significantly stronger than controls. Using logistic regression, a multi-attribute classifier was derived that accurately distinguished cases from controls (area under curve of 0.96).ConclusionsComputational EEG features successfully distinguish ES patients from controls in a large, blinded study.SignificanceThese objective EEG markers, in combination with other clinical factors, may speed the diagnosis and treatment of the disease, thereby improving long-term outcomes.HighlightsObjective computational EEG features may aid diagnosis of epileptic spasms (ES)ES EEG has increased delta and theta power and decreased entropy relative to controlsStronger functional connectivity networks differentiate ES patients from controls
Predictive attenuation of touch and tactile gating are distinct perceptual phenomena
Authors: Kilteni Konstantina , Ehrsson H. Henrik 
Published: November 2020

AbstractIn recent decades, research on somatosensory perception has led to two important observations. First, self-generated touches that are predicted by voluntary movements become attenuated compared to externally generated touches of the same intensity (attenuation). Second, externally generated touches feel weaker and are more difficult to detect during movement than at rest (gating). Currently, researchers often consider gating and attenuation the same suppression process; however, this assumption is unwarranted because, despite more than forty years of research, no study has combined them in a single paradigm. We quantified how people perceive self-generated and externally generated touches during movement and rest. We show that whereas voluntary movement gates the precision of both self-generated and externally generated touch, the amplitude of self-generated touch is robustly attenuated compared to externally generated touch. Furthermore, attenuation and gating do not interact and are not correlated, and we conclude that they represent distinct perceptual phenomena.