bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical property alterations across the cerebral cortex due to Alzheimer’s disease
Authors: Hiscox Lucy V , Johnson Curtis L , McGarry Matthew D J , Marshall Helen , Ritchie Craig W , van Beek Edwin J R , Roberts Neil , Starr John M
Published: December 2019

Alzheimer’s disease is a personally devastating neurodegenerative disorder and a major public health concern. There is an urgent need for medical imaging techniques that better characterize the early stages and monitor the progression of the disease. Magnetic resonance elastography (MRE) is a relatively new and highly sensitive MRI technique that can non-invasively assess tissue microstructural integrity via measurement of brain viscoelastic mechanical properties. For the first time, we use high-resolution MRE methods to conduct a voxel-wise MRE investigation and state-of-the-art post hoc region of interest analysis of the viscoelastic properties of the cerebral cortex in patients with Alzheimer’s disease (N = 11) compared with cognitively healthy older adults (N = 12). We replicated previous findings that have reported significant volume and stiffness reductions at the whole-brain level. Significant reductions in volume were also observed in Alzheimer’s disease when white matter, cortical grey matter and subcortical grey matter compartments were considered separately; lower stiffness was also observed in white matter and cortical grey matter, but not in subcortical grey matter. Voxel-based morphometry of both cortical and subcortical grey matter revealed localized reductions in volume due to Alzheimer’s disease in the hippocampus, fusiform, middle, superior temporal gyri and precuneus. Similarly, voxel-based MRE identified lower stiffness in the middle and superior temporal gyri and precuneus, although the spatial distribution of these effects was not identical to the pattern of volume reduction. Notably, MRE additionally identified stiffness deficits in the operculum and precentral gyrus located within the frontal lobe; regions that did not undergo volume loss identified through voxel-based morphometry. Voxel-based-morphometry and voxel-based MRE results were confirmed by a complementary post hoc region-of-interest approach in native space where the viscoelastic changes remained significant even after statistically controlling for regional volumes. The pattern of reduction in cortical stiffness observed in Alzheimer’s disease patients raises the possibility that MRE may provide unique insights regarding the neural mechanisms which underlie the development and progression of the disease. The measured mechanical property changes that we have observed warrant further exploration to investigate the diagnostic usefulness of MRE in cases of Alzheimer’s disease and other dementias.
Management of pulmonary arterial hypertension in patients aged over 65 years
Authors: Sitbon Olivier , Howard Luke
Published: December 2019

Historically, pulmonary arterial hypertension (PAH) has been considered a disease of young adults, but over the last three decades, the average age at diagnosis has increased, presenting clinicians with some unique challenges. Clinical symptoms of PAH, including shortness of breath and reduced functional capacity, are not specific for the disease and may be present in older patients because of their age or as a result of comorbid conditions. Eliminating other causes for these symptoms can delay PAH diagnosis and initiation of PAH-specific treatment compared with younger patients. Currently, there are no specific guidelines relating to PAH in older patients and existing guidelines for identifying patients at potential risk of PAH may not be appropriate for patients aged over 65 years. Even though older patients tend to be diagnosed with more advanced symptoms, and evidence suggests that they are less responsive to PAH-specific therapies, treatment is often less aggressive than in younger patients. Even after adjusting for age, survival rates remain disproportionately lower in the older vs. younger PAH populations. Specific guidelines for diagnosis and treatment of older patients with PAH are needed to improve care and outcomes in this growing population. This review aims to assess the challenges associated with diagnosing and managing PAH in older patients, based on literature searches, authors’ experiences, and expert opinions.
The revised definition of pulmonary hypertension: exploring the impact on patient management
Authors: Simonneau Gérald , Hoeper Marius M
Published: December 2019

At the 6th World Symposium on Pulmonary Hypertension (PH), it was proposed that the mean pulmonary arterial pressure (mPAP) threshold used to define PH should be lowered from ≥25 mmHg to >20 mmHg. The rationale for this change is that the ≥25 mmHg threshold is arbitrary, whereas the revised threshold is based on scientific evidence. For the definition of all forms of pre-capillary PH, the inclusion of a pulmonary vascular resistance (PVR) ≥3 Wood Units was also proposed, placing greater emphasis on an elevated PVR to identify pulmonary vascular disease. Here, we discuss the possible impact of the revised definition of PH on future clinical management. This change may facilitate earlier PH detection, particularly in at-risk patient groups that are already undergoing screening programmes, e.g. those with systemic sclerosis or mutations associated with PH. As an mPAP above the upper limit of normal (>20 mmHg) but <25 mmHg is associated with increased risk of morbidity and mortality compared with a normal mPAP, early identification of patients in this group is important to enable close monitoring and timely treatment initiation once clinically indicated. Treatments currently approved for PH are not necessarily suitable for patients with an mPAP 21–24 mmHg, as the management of this group has not been widely examined. The revised definition may facilitate inclusion of these patients in prospective trials, allowing the evaluation of appropriate management strategies.
Pulmonary arterial hypertension populations of special interest: portopulmonary hypertension and pulmonary arterial hypertension associated with congenital heart disease
Authors: Savale Laurent , Manes Alessandra
Published: December 2019

Guidelines exist for management of pulmonary arterial hypertension (PAH), but information is limited for certain patient subgroups, including adults with portopulmonary hypertension (PoPH) or with PAH associated with congenital heart disease (PAH-CHD). This article discusses screening, clinical management, and prognosis in PoPH and PAH-CHD and, as such, considers the most recent clinical data and expert advice. A multidisciplinary consultation and follow-up by specialists are crucial for management of both PoPH and PAH-CHD, but each condition presents with unique challenges. Development of PoPH most commonly occurs among patients with liver cirrhosis. Initially, patients may be asymptomatic for PoPH and, if untreated, survival with PoPH is generally worse than with idiopathic PAH (IPAH), so early identification with screening is crucial. PoPH can be managed with PAH-specific pharmacological therapy, and resolution is possible in some patients with liver transplantation. With PAH-CHD, survival rates are typically higher than with IPAH but vary across the four subtypes: Eisenmenger syndrome, systemic-to-pulmonary shunts, small cardiac defects, and corrected defects. Screening is also crucial and, in patients who undergo correction of CHD, the presence of PAH should be assessed immediately after repair and throughout their long-term follow-up, with frequency of assessments determined by the patient’s characteristics at the time of correction. Early screening for PAH in patients with portal hypertension or CHD, and multidisciplinary management of PoPH or PAH-CHD are important for the best patient outcomes.
Educational differences in acute infectious diseases in the Netherlands: results from a nationwide health survey
Authors: de Gier Brechje , Houben - van Herten Marieke , Uiters Ellen , Hahné Susan J M
Published: December 2019

Background

It is unclear to what extent socioeconomic inequalities exist in common infectious diseases in high-income countries. We aimed to explore educational differences in five common acute infectious diseases in adults in the Netherlands.

Methods

As part of a year-round repeated cross-sectional health survey, adults aged 25 and older were asked if they had experienced acute upper or lower respiratory tract infections, acute otitis media, urinary tract infections or gastro-enteritis in the two previous months. If so, participants were asked whether they had consulted their general practitioner and if they had been unable to perform their normal daily activities. These outcomes were analyzed per highest attained level of education.

Results

Data of 18 629 survey respondents were used in the analyses. People with a low educational level had lower odds of upper respiratory tract infections (OR 0.88, 95% CI 0.81–0.95), but higher odds of lower respiratory tract infections (OR 1.57, 95% CI 1.16–2.11). After adjustment for several covariates, the differences in upper respiratory tract infections remained statistically significant (aOR 0.84, 95% CI 0.77–0.91). The educational differences in lower respiratory tract infections were mitigated by adjusting for chronic diseases and health behaviours. For all infectious diseases, the likelihood of general practitioner consultation was highest for the lower educated group. Inability to work or perform normal daily activities due to an infectious disease was similar across all levels of education.

Conclusion

This study shows that educational differences in incidence and care seeking behaviours exist for common acute infectious diseases in the Netherlands.
Migrant Advocacy under Austerity: Transforming Solidarity in the Greek-Refugee Regime
Authors: Pendakis Katherine L
Published: December 2019

With the United Nations High Commissioner for Refugees’ declaration of an emergency in 2016, Thessaloniki’s refugee regime began to develop rapidly. Local non-governmental organizations (NGOs) were transformed from underfunded initiatives to institutions managing large budgets and requiring staff with intercultural competencies and experience with migrant populations. For this, they turned to the ‘lost generation’— Greek youth who had come of age during the economic crisis and who had formed close relationships with migrants through political mobilizations and local solidarity networks that had sprung up in response to widespread austerity. In this article, I ask: How is the conversion of young ‘radicals’ from ‘anti-state’ activist networks into NGO representatives achieved? How does this transition impact former activists’ relationships with migrants and how do former activists make sense of this change? What, if anything, makes this a ‘Thessaloniki story’? My argument is three-fold. First, the conversion of activists into NGO representatives is made possible by a combination of young people’s exclusion from economic opportunities and the state’s disciplining of forms of solidarity that exist outside of the refugee regime. Second, the refugee regime converts solidarity established through political struggle into a form of human capital that affords former activists social mobility. Existing solidarity between former activists and migrants is undermined as a result. Third, on account of their new role as gatekeepers in NGOs, former activists struggle to offer a compelling narrative of continuity with their left-wing identity and their politicized commitment to migrants. In doing so, they rely on identifiable forms of boundary work and justification.
Lethality caused by ADP-glucose accumulation is suppressed by salt-induced carbon flux redirection in cyanobacteria
Authors: Díaz-Troya Sandra , Roldán Miguel , Mallén-Ponce Manuel J , Ortega-Martínez Pablo , Florencio Francisco J
Published: December 2019

Cyanobacteria are widely distributed photosynthetic organisms. During the day they store carbon, mainly as glycogen, to provide the energy and carbon source they require for maintenance during the night. Here, we generate a mutant strain of the freshwater cyanobacterium Synechocystis sp. PCC 6803 lacking both glycogen synthases. This mutant has a lethal phenotype due to massive accumulation of ADP-glucose, the substrate of glycogen synthases. This accumulation leads to alterations in its photosynthetic capacity and a dramatic decrease in the adenylate energy charge of the cell to values as low as 0.1. Lack of ADP-glucose pyrophosphorylase, the enzyme responsible for ADP-glucose synthesis, or reintroduction of any of the glycogen synthases abolishes the lethal phenotype. Viability of the glycogen synthase mutant is also fully recovered in NaCl-supplemented medium, which redirects the surplus of ADP-glucose to synthesize the osmolite glucosylglycerol. This alternative metabolic sink also suppresses phenotypes associated with the defective response to nitrogen deprivation characteristic of glycogen-less mutants, restoring the capacity to degrade phycobiliproteins. Thus, our system is an excellent example of how inadequate management of the adenine nucleotide pools results in a lethal phenotype, and the influence of metabolic carbon flux in cell viability and fitness.
Search for the optical counterpart of the GW170814 gravitational wave event with the VLT Survey Telescope
Authors: Grado A , Cappellaro E , Covino S , Getman F , Greco G , Limatola L , Yang S , Amati L , Benetti S , Branchesi M , Brocato E , Botticella M , Campana S , Cantiello M , Dadina M , D’Ammando F , De Cesare G , D’Elia V , Della Valle M , Iodice E , Longo G , Mapelli M , Masetti N , Nicastro L , Palazzi E , Possenti A , Radovich M , Rossi A , Salvaterra R , Stella L , Stratta G , Testa V , Tomasella L
Published: December 2019

We report on the search for the optical counterpart of the gravitational event GW170814, which was carried out with the VLT Survey Telescope (VST) by the GRAvitational Wave Inaf TeAm. Observations started 17.5 h after the Laser Interferometer Gravitational-wave Observatory (LIGO) and Virgo alert and we covered an area of 99 deg2 that encloses $\sim 77{{\ \rm per\ cent}}$ and $\sim 59{{\ \rm per\ cent}}$ of the initial and refined localization probability regions, respectively. A total of six epochs were secured over nearly two months. The survey reached an average limiting magnitude of 22 AB mag in the r band. After assuming the model described in Perna, Lazzati & Farr, that derives as possible optical counterpart of a BBH (binary black hole) event a transient source declining in about one day, we have computed a survey efficiency of about $5{{\ \rm per\ cent}}$. This paper describes the VST observational strategy and the results obtained by our analysis pipelines developed to search for optical transients in multi-epoch images. We report the catalogue of the candidates with possible identifications based on light-curve fitting. We have identified two dozens of SNe, nine AGNs, and one QSO. Nineteen transients characterized by a single detection were not classified. We have restricted our analysis only to the candidates that fall into the refined localization map. None out of 39 left candidates could be positively associated with GW170814. This result implies that the possible emission of optical radiation from a BBH merger had to be fainter than r ∼ 22 (Loptical ∼ 1.4 × 1042 erg s−1) on a time interval ranging from a few hours up to two months after the gravitational wave event.
Effect of turbulent pressure on the origin of low-frequency quasi-periodic oscillations in rotating black holes
Authors: Mondal Santanu
Published: December 2019

Quasi-periodic oscillation (QPO), particularly of low frequency (LF), is a very obvious feature of outbursting black hole candidates. The association of QPOs in a specific spectral state and their transition with states make them a key ingredient in understanding the underlying physical processes that produce them. Observations have revealed that generally, in the hard spectral state of the outburst, the size of the Compton cloud is relatively bigger, which produces low-frequency QPOs (LFQPOs). In progressive days increased cooling shrinks the area of the cloud, the inner edge of the disc comes close to the black holes, and produces higher frequency QPOs. However, rotating black holes with higher spin values are likely to produce LFQPOs even if their inner edge of the disc is closer to the hole. Here, for the first time, we address the issue, solving hydrodynamic flow equations in the presence of qualitative turbulent pressure and cooling in pseudo-Kerr geometry. Increasing turbulence slackens the infalling flow, thus the infall time becomes longer, producing LFQPOs. Our study discovers that the effect of turbulence modifies LFQPOs value significantly, by a factor of a few lower throughout the angular momentum distribution of the flow. We find a strong correlation between the turbulence and the spin parameter of the hole. Finally, we discuss the observed results in light of the present solution.
Can close-in giant exoplanets preserve detectable moons?
Authors: Sucerquia Mario , Ramírez Vanesa , Alvarado-Montes Jaime A , Zuluaga Jorge I
Published: December 2019

Exoplanet discoveries have motivated numerous efforts to find unseen populations of exomoons, yet they have been unsuccessful. A plausible explanation is that most discovered planets are located on close-in orbits, which would make their moons prone to tidal evolution and orbital detachment. In recent models of tidally driven migration of exomoons, evolving planets might prevent what was considered their most plausible fate (i.e. colliding against their host planet), favouring scenarios where moons are pushed away and reach what we define as the satellite tidal orbital parking distance ($a_{\rm \mathrm{stop}}$), which is often within the critical limit for unstable orbits and depends mainly on the system’s initial conditions: mass ratio, semimajor axes, and rotational rates. Using semi-analytical calculations and numerical simulations, we calculate $a_{\rm \mathrm{stop}}$ for different initial system parameters and constrain the transit detectability of exomoons around close-in planets. We found that systems with Mm/Mp ≥ 10−4, which are less likely to form, are also stable and detectable with present facilities (e.g. Kepler and TESS) through their direct and secondary effects in planet + moon transit, as they are massive, oversized, and migrate slowly. In contrast, systems with lower moon-to-planet mass ratios are ephemeral and hardly detectable. Moreover, any detection, confirmation, and full characterization would require both the short cadence capabilities of TESS and high photometric sensitivity of ground-based observatories. Finally, despite the shortage of discovered long-period planets in currently available data bases, the tidal migration model adopted in this work supports the idea that they are more likely to host the first detectable exomoon.
Information theoretic bounds on cosmic string detection in CMB maps with noise
Authors: Ciuca Razvan , Hernández Oscar F
Published: December 2019

We use a convolutional neural network to study cosmic string detection in cosmic microwave background (CMB) flat sky maps with Nambu–Goto strings. On noiseless maps, we can measure string tensions down to order 10−9, however when noise is included we are unable to measure string tensions below 10−7. Motivated by this impasse, we derive an information theoretic bound on the detection of the cosmic string tension Gμ from CMB maps. In particular, we bound the information entropy of the posterior distribution of Gμ in terms of the resolution, noise level and total survey area of the CMB map. We evaluate these bounds for the ACT, SPT-3G, Simons Observatory, Cosmic Origins Explorer, and CMB-S4 experiments. These bounds cannot be saturated by any method.
Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes
Authors: Kumar Rajendra , Chand Karam , Bhowmik Sudipta , Das Rabindra Nath , Bhattacharjee Snehasish , Hedenström Mattias , Chorell Erik
Published: December 2019

G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.
Co-use and Mixing Tobacco With Cannabis Among Ontario Adults
Authors: Jayakumar Navitha , Chaiton Michael , Goodwin Renee , Schwartz Robert , O’Connor Shawn , Kaufman Pamela
Published: December 2019

Introduction

The legalization of nonmedical cannabis in 2018 may have important implications for tobacco use in Canada. There is a risk of renormalizing tobacco use with co-use of tobacco and cannabis introducing nontobacco users to tobacco. Co-use is the use of both substances by the same individual at the same time or on different occasions, as well as mixed together. This study assessed the prevalence of co-use and mixing of tobacco and cannabis among Ontario adults and the characteristics of the users.

Aims and Methods

Data from the 1996 to 2017 cycles of the Centre for Addiction and Mental Health Monitor (n = 4481) were used to examine trends in prevalence and the proportion of Ontario adults co-using and mixing tobacco and cannabis. Logistic regression was used to study associations between user characteristics and co-use and mixing.

Results

Co-use of cigarettes and cannabis among cannabis users declined from 59.8% in 1996 to 41.7% in 2017. Past-year e-cigarette use was the only predictor of co-use. From 2015 to 2017, 31.1% (95% confidence interval 27.0, 35.9) of Ontario adults who used cannabis reported mixing it with tobacco in the past year. Being white, past-year e-cigarette use, having moderate or high nicotine dependence, and having moderate or high risk for cannabis problems were significant predictors of mixing among cannabis users.

Conclusion

Given the well-established negative health effects associated with tobacco use, alongside a growing evidence base for negative health effects of cannabis smoking, co-use and mixing could pose a considerable public health concern in the context of legalization.

Implications

Considerable effort has been expended to reduce tobacco smoking. However, current efforts to reduce tobacco smoking may be diminished since this study found the prevalence of mixing tobacco and cannabis among cannabis users in Ontario to be higher than expected. Mixing tobacco and cannabis may introduce nontobacco smokers to tobacco, exposing them to health risks associated with both cannabis and tobacco smoke. Therefore, there is a need to monitor changes in tobacco use and understanding implications for tobacco control and cessation programs within the changing environment of cannabis legalization in Canada and other jurisdictions.
The Effectiveness of Cervical Medial Branch Radiofrequency Ablation for Chronic Facet Joint Syndrome in Patients Selected by a Practical Medial Branch Block Paradigm
Authors: Burnham Taylor , Conger Aaron , Salazar Fabio , Petersen Russell , Kendall Richard , Cunningham Shellie , Teramoto Masaru , McCormick Zachary L
Published: December 2019

Background

Cervical medial branch radiofrequency ablation (CMBRFA) is an effective treatment for facetogenic pain in patients selected by Spine Intervention Society (SIS) guidelines of 100% symptom improvement with dual medial branch blocks (MBBs) ± placebo block. Patient selection for CMBRFA using ≥80% symptom improvement after dual concordant MBBs is common; however, this has not been studied.

Objective

To evaluate the effectiveness of CMBRFA and compare outcomes in individuals selected by 80–99% vs 100% symptom improvement with dual concordant MBBs.

Design

Cross-sectional cohort study.

Methods

Medical records of 87 consecutive patients were reviewed; 50 met inclusion criteria. A standardized telephone survey was performed at six or more months post-CMBRFA to query numerical rating scale (NRS) pain and patient global impression of change (PGIC) scores. The primary outcomes were the proportion of patients reporting ≥50% reduction of index pain.

Results

At a mean follow-up time of 16.9 ± 12.7 months, 54% (95% confidence interval [CI] = 35–73%) and 54% (95% CI = 32–74%) of the 80–99% and 100% MBBs groups, respectively, reported ≥50% pain reduction. Between-group comparison showed a relative risk of 0.99 (95% CI = 0.59–1.66) for meeting the primary outcome. Seventy percent (95% CI = 56–81%) of patients reported a PGIC score consistent with “improved or very much improved” at follow-up.

Conclusions

CMBRFA is an effective treatment in patients who report ≥80% symptom relief with dual concordant MBBs. The present study demonstrated an overall ≥50% pain reduction rate of 54% and no significant difference between those selected by 80–99% vs 100% symptom relief with dual concordant MBBs.
Democratizing health system data to impact social and environmental health contexts: a novel collaborative community data-sharing model
Authors: Boulware L E , Harris G B , Harewood P , Johnson F F , Maxson P , Bhavsar N , Blackwelder S S , Poley S S , Arnold K , Akindele B , Ferranti J , Lyn M
Published: December 2019

Background

Community health data are infrequently viewed in the context of social and environmental health determinants. We developed a novel data-sharing model to democratize health system data and to facilitate community and population health improvement.

Methods

Durham County, the City of Durham in North Carolina, Durham health systems and other stakeholders have developed a data-sharing model to inform local community health efforts. Aggregated health system data obtained through clinical encounters are shared publicly, providing data on the prevalence of health conditions of interest to the community.

Results

A community-owned web platform called the Durham Neighborhood Compass provides aggregate health data (e.g. on diabetes, heart disease, stroke and other conditions of interest) in the context of neighborhood social (e.g. income distribution, education level, demographics) and environmental (e.g. housing prices, crime rates, travel routes, school quality, grocery store proximity) contexts. Health data are aggregated annually to help community stakeholders track changes in health and health contexts over time.

Conclusions

The Durham Neighborhood Compass is among the first collaborative public efforts to democratize health system data in the context of social and environmental health determinants. This model could be adapted elsewhere to support local community and population health improvement initiatives.
Self-Preservation in the Workplace: The Importance of Well-Being for Social Work Practitioners and Field Supervisors
Authors: Martin Elisa M , Myers Karen , Brickman Kirstiana
Published: December 2019

The risks in the human services workplace to social workers’ emotional, psychological, and physical well-being is well known. Self-care is seen as a way to minimize workplace risks, including burnout, compassion fatigue, secondary traumatic stress, and vicarious traumatization. This article examines the reported self-care practices of social work practitioners and their agencies, and the barriers that get in the way. Forty-two participants worked in agency settings and supervised students. All reported engaging in some type of self-care practice, and almost all reported some type of support from their workplace; however, 38 reported barriers to self-care. Even with self-care practices in place personally and in the workplace, obstacles remain. Social work educators need to be cognizant of these factors to ensure that field supervisors are well supported in their own self-care practices and are equipped to assist students in developing these positive practices early in their careers to help sustain workers in the social work profession.
Triclocarban Exposure Exaggerates Spontaneous Colonic Inflammation in Il-10−/− Mice
Authors: Xie Minhao , Zhang Hongna , Wang Weicang , Sherman Heather L , Minter Lisa M , Cai Zongwei , Zhang Guodong
Published: December 2019

Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a high-volume chemical used as an antimicrobial ingredient in many consumer and personal care products. In 2016, the Food and Drug Administration removed TCC from over-the-counter hand washing products. However, TCC remains approved to use in many other products and is a ubiquitous contaminant in the environment; furthermore, many common food crops can efficiently accumulate environmental TCC, resulting in potential human exposure through oral ingestion of contaminated food products. Therefore, human exposure to TCC could be a long-lasting and serious problem. A better understanding of its impact on human health could lead to important impact for public health and regulatory policy. Using a spontaneous colonic inflammation model in Il-10−/− mice, here we demonstrate that exposure to TCC, at doses relevant to human exposure, exaggerates spontaneous colonic inflammation in Il-10−/− mice, with reduced colon length, increase fecal concentration of lipocalin 2, enhanced gene expression of Il-6 and Ifn-γ in the colon, and exaggerated crypt damage in the colon. Collectively, these results support that TCC could be a potential environmental risk factor of colitis and associated gut diseases.
Multilevel Disaster Simulation in Nursing: Lessons Learned in Undergraduate and Nurse Practitioner Student Collaboration
Authors: Primeau Marlena Seibert , Benton Anna M.
Published: December 2019

Disaster simulation in nursing education has become fairly common, including both single discipline and interprofessional collaborative events. However, there is a distinct lack of information on disaster simulation involving intraprofessional, multilevel nursing students working collaboratively. Our established undergraduate disaster simulation is a required event for our final-semester senior nursing students. To collect baseline information, a quality improvement program was initiated during one simulation, with six graduate family nurse practitioner students involved as on-scene clinicians in the clinical areas. We found that several basic assumptions were incorrect and that adjustments in training were needed to make this collaborative simulation successful.
Early Prediction of Sepsis From Clinical Data: The PhysioNet/Computing in Cardiology Challenge 2019
Authors: Reyna Matthew A. , Josef Christopher S. , Jeter Russell , Shashikumar Supreeth P. , Westover M. Brandon , Nemati Shamim , Clifford Gari D. , Sharma Ashish
Published: December 2019

Objectives:

Sepsis is a major public health concern with significant morbidity, mortality, and healthcare expenses. Early detection and antibiotic treatment of sepsis improve outcomes. However, although professional critical care societies have proposed new clinical criteria that aid sepsis recognition, the fundamental need for early detection and treatment remains unmet. In response, researchers have proposed algorithms for early sepsis detection, but directly comparing such methods has not been possible because of different patient cohorts, clinical variables and sepsis criteria, prediction tasks, evaluation metrics, and other differences. To address these issues, the PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data.

Design:

Participants submitted containerized algorithms to a cloud-based testing environment, where we graded entries for their binary classification performance using a novel clinical utility-based evaluation metric. We designed this scoring function specifically for the Challenge to reward algorithms for early predictions and penalize them for late or missed predictions and for false alarms.

Setting:

ICUs in three separate hospital systems. We shared data from two systems publicly and sequestered data from all three systems for scoring.

Patients:

We sourced over 60,000 ICU patients with up to 40 clinical variables for each hour of a patient’s ICU stay. We applied Sepsis-3 clinical criteria for sepsis onset.

Interventions:

None.

Measurements and Main Results:

A total of 104 groups from academia and industry participated, contributing 853 submissions. Furthermore, 90 abstracts based on Challenge entries were accepted for presentation at Computing in Cardiology.

Conclusions:

Diverse computational approaches predict the onset of sepsis several hours before clinical recognition, but generalizability to different hospital systems remains a challenge.
Molecular prediction of metastasis in cutaneous squamous cell carcinoma
Authors: Mulvaney Patrick M. , Schmults Chrysalyne D.
Published: December 2019

Purpose of review

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent malignancy frequently occurring on body surfaces chronically exposed to ultraviolet radiation. While a large majority of tumors remain localized to the skin and immediate subcutaneous tissue and are cured with surgical excision, a small subset of patients with cSCC will develop metastatic disease. Risk stratification for cSCC is performed using clinical staging systems, but given a high mutational burden and advances in targeted and immunotherapy, there is growing interest in molecular predictors of high-risk disease.

Recent findings

Recent literature on the risk for metastasis in cSCC includes notable findings in genes involved in cell-cycle regulation, tumor suppression, tissue invasion and microenvironment, interactions with the host-immune system, and epigenetic regulation.

cSCC is a highly mutated tumor with complex carcinogenesis. Regulators of tumor growth and local invasion are numerous and increasingly well-understood but drivers of metastasis are less established. Areas of importance include central system regulators (NOTCH, miRNAs), proteins involved in tissue invasion (podoplanin, E-cadherin), and targets of existing and emerging therapeutics (PD-1, epidermal growth factor receptor). Given the complexity of cSCC carcinogenesis, the use of machine learning algorithms and computational genomics may provide ultimate insight and prospective studies are needed to verify clinical relevance.
Molecular characterization of endometrial cancer and therapeutic implications
Authors: Winterhoff Boris , Thomaier Lauren , Mullany Sally , Powell Matthew A.
Published: December 2019

Purpose of review

The present article reviews molecular subtyping and genomic characterization of endometrial carcinoma, and the associated therapeutic and prognostic implications.

Recent findings

Endometrial cancer has historically been classified through histology into endometrioid and nonendometrioid subtypes with poor prognostic predictability. Molecular classification through genomic analysis now allows for a major advance in characterization. Four distinct subgroups have been identified: polymerase (POLE) ultramutated, microsatellite unstable, copy number-low--microsatellite stable, and copy number-high—‘serous-like’. These subtypes have prognostic implications and may aid in the identification of early-stage patients who are at high risk for recurrence. Through analysis of surrogate markers (POLE, MSI, and p53) and other validated molecular alterations (L1CAM), it is possible to obtain an integrated molecular risk profile that relates to prognosis. Studies utilizing this risk profile in order to identify patients who may benefit from adjuvant treatment for early-stage disease are on-going.

Molecular characterization of endometrial cancer into subgroups has enhanced prognostic and therapeutic implications, contrary to traditional risk stratification. Further development of an integrated molecular risk profile may identify patients who could most benefit from adjuvant treatment following surgery and tailor treatment decisions in the recurrent setting.
The Role of Obesity in Iatrogenic Encephaloceles of the Temporal Bone
Authors: Lindquist Nathan R. , Appelbaum Eric N. , Sweeney Alex D. , Vrabec Jeffrey T.
Published: December 2019

Objective:

Acquired encephaloceles of the temporal bone may be traumatic, spontaneous, or from chronic ear disease or previous surgery. Iatrogenic encephaloceles arise in the setting of previous mastoidectomy and traditionally involve both bony dehiscence and dural injury. We aim to classify and analyze the pathogenesis, clinical presentation, and treatment options for patients with iatrogenic tegmen defects and encephaloceles of the temporal bone.

Study Design:

Retrospective chart review.

Setting:

Single tertiary academic center.

Patients:

Subjects with iatrogenic tegmen defects and encephaloceles of the temporal bone were included.

Intervention:

Patient demographics, history, symptoms, radiographic data, intraoperative findings, management, follow-up, and outcomes were recorded.

Outcome Measures:

Primary outcome measures included patient characteristics, time from primary otologic surgery to surgical repair, location of the defect, and management strategy including surgical approach, methods, and follow-up.

Results:

Iatrogenic tegmen injuries or encephaloceles were identified in 18 patients and divided into intentional or unintentional. The latter group presented immediately, early, or late, as determined by intraoperative identification or from delayed symptoms. Eleven patients presented late with previously unrecognized encephaloceles. Compared with patients presenting with incidentally noted tegmen dehiscence during revision mastoidectomy, a significant proportion of patients with late encephaloceles had BMI ≥30 kg/m2 (p = 0.03).

Conclusion:

The majority of iatrogenic encephaloceles are unintentional, unrecognized, and may present many years after primary surgery. Similar to spontaneous encephaloceles of the temporal bone, obesity is associated with iatrogenic encephaloceles, although the rate of progression and timing is unclear. We recommend primary repair of any unintentional tegmen defect encountered during mastoid surgery, especially in obese patients.
Reliability of Tablet-based Hearing Testing in Nicaraguan Schoolchildren: A Detailed Analysis
Authors: Magro Isabelle , Clavier Odile , Mojica Karen , Rieke Catherine , Eisen Eric , Fried Debra , Stein-Meyers Anita , Fellows Abigail , Buckey Jay , Saunders James
Published: December 2019

Objective:

Determine whether an electronic tablet-based Wireless Automated Hearing-Test System can perform high-quality audiometry to assess schoolchildren for hearing loss in the field in Nicaragua.

Study Design:

Cross-sectional.

Setting:

A school and hospital-based audiology clinic in Jinotega, Nicaragua.

Subjects and Methods:

Second and third graders (n = 120) were randomly selected for hearing testing in a school. Air conduction hearing thresholds were obtained bilaterally using a Wireless Automated Hearing-Test System at 1000, 2000, and 4000 Hz. Referral criteria were set at more than 25 dBHL at one or more frequencies. A cohort of children was retested with conventional audiometry in a hospital-based sound booth. Factors influencing false-positive examinations, including ambient noise and behavior, were examined.

Results:

All children with hearing loss were detected using an automated, manual, or two-step (those referred from automated testing were tested manually) protocol in the school (sensitivity = 100%). Specificity was 76% for automated testing, 97% for manual testing, and 99% for the two-step protocol. The variability between thresholds obtained with automated testing was greater than manual testing when compared with conventional audiometry. The percentage of participant responses when no stimulus tone was presented during automated testing was higher in children with false-positive examinations.

Conclusion:

A Wireless Automated Hearing-Test System identified all children with hearing loss in a challenging field setting. A two-step protocol (those referred from automated testing are tested manually) reduced false-positive examinations and unnecessary referrals. Children who respond frequently when no tone is presented are more likely to have false-positive automated examinations and should be tested manually.
Serum Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor–binding Protein 2 as a Novel Biomarker in the Detection of Pancreatic Adenocarcinoma
Authors: Wlodarczyk Barbara , Borkowska Anna , Wlodarczyk Przemyslaw , Malecka-Panas Ewa , Gasiorowska Anita
Published: December 2019

Background:

Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor–binding protein 2 (IGFBP-2) are proteins that belong to the IGF axis, which is involved in glucose and lipid metabolism and may as well promote carcinogenesis.

Goals:

The aim of this study was to evaluate the serum concentration levels of IGF-1 and IGFBP-2 in patients with newly diagnosed pancreatic adenocarcinoma (PDAC) to verify their possible role in the diagnosis of the disease.

Study:

The study included 69 patients with PDAC and 20 healthy controls. The concentrations of IGF-1 and IGFBP-2 were estimated by means of ELISA. The study protocol was approved by the Bioethics Committee at the Medical University of Lodz in Poland.

Results:

PDAC patients compared with controls have a significantly lower mean serum IGF-1 level (45.83±30.03 vs. 70.66±60.57 ng/mL; P<0.0001). In contrast, in PDAC patients, the mean IGFBP-2 level was significantly higher compared with the control group (225.06±86.37 vs. 51.92±29.40 ng/mL; P<0.0001). The results show that, at the 0.01 sensitivity level, the IGF-1/IGFBP-2 ratio <0.85 points indicates PDAC presence. At this level of sensitivity, the test has a specificity of 0.097 (α=0.01; β=0.097; IGF-1/IGFBP-2≤0.85).

Conclusions:

Our results show that IGF-1 to IGFBP-2 ratio ≤0.85 may be a powerful PDAC indicator. Further studies in this area in a larger patient group are necessary to confirm our findings.
Comparison of the effectiveness and outcome of microendoscopic and open discectomy in patients suffering from lumbar disc herniation
Authors: Yadav Ram Ishwar , Long Ling , Yanming Cao
Published: December 2019

Background:

The purpose of our study is to compare the outcomes and effectiveness of MED vs OLD for lumbar disc herniation.

Objectives:

To identify the functional outcomes in terms of ODI score, VAS score complications in terms of intraoperative blood loss, use of general anesthesia, and morbidity in terms of total hospital stay between MED and OLD.

Methods:

In our randomized prospective study we analyzed 60 patients with clinical signs and symptoms with 2 weeks of failed conservative treatment plus MRI or CT scan findings of lumbar disc herniation who underwent MED and OLD. The study was undertaken from November 2017 to January 2019 at Guangzhou Medical University of Second Affiliated Hospital, department of orthopedic surgery in spinal Unit, Guangzhou, China. Patients were divided into 2 groups i.e. who underwent MED group and the OLD group then we compared the preoperative and postoperative ODI and VAS score, duration of total hospital stay, intraoperative blood loss, and operation time.

Results:

We evaluated 60 patients. Among them, 30 underwent MED (15 female and 15 male) and 30 underwent OLD 14 male 16 female. Surgical and anesthesia time was significantly shorter, blood loss and hospital stay were significantly reduced in patients having MED than OLD (<0.005). The improvement in the ODI in both groups was clinically significant and statistically (P < .005) at postoperative 1st day (with greater improvement in the MED group), at 6 weeks (P > .005), month 6 (>0.005) statistically no significant. The clinical improvement was similar in both groups. VAS and ODI scores improved significantly postoperatively in both groups. However, the MED group was superior to the OLD group with less time in bed, shorter operation time, less blood loss which is clinically and statistically significant (P < .05).

Conclusions:

The standard surgical treatment of lumbar disc herniation has been open discectomy but there has been a trend towards minimally invasive procedures. MED for lumbar spine disc herniation is a well-known but developing field, which is increasingly spreading in the last few years. The success rate of MED is about approximately 90%. Both methods are equally effective in relieving radicular pain. MED was superior in terms of total hospital stay, morbidity, and earlier return to work and anesthetic exposure, blood loss, intra-op time comparing to OLD. MED is a safe and effective alternative to conventional OLD for patients with lumbar disc herniation.
Serum microRNA-135a as a diagnostic biomarker in non-small cell lung cancer
Authors: Zou Yuanwu , Jing Chengbao , Liu Li , Wang Ting
Published: December 2019

The purpose of our research was to evaluate diagnostic performance of serum microRNA-135a (miR-135a) in non-small cell lung cancer (NSCLC).

Quantitative real time-polymerase chain reaction was employed to detect the expression serum of miR-135a in NSCLC patients and controls. The influence of serum miR-135a level on clinical characteristics of NSCLC patients was explored through the Chi-square test. Serum carcinoembryonic antigen (CEA) level was estimated via enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was plotted to elucidate diagnostic roles of serum miR-135a and CEA in NSCLC.

The expression level of serum miR-135a was significantly lower in NSCLC patients than in healthy controls (0.40 ± 0.29 vs 1.00 ± 0.40, P < .001). Moreover, miR-135a expression was related to lymph node metastasis (P = .021), tumor differentiation (P = .020), and tumor node metastasis stage (P = .031). ROC curve showed serum miR-135a level could discriminate NSCLC patients from healthy controls (P < .0001) with a corresponding cutoff value of 0.665, and a sensitivity and specificity of 81.3% and 83.1%, respectively. The area under the curve was 0.888. In diagnosis analysis on the combination of miR-135a and CEA, when its specificity was maintained at 90%, diagnosis cut-off point reached 0.678.

Serum miR-135a level is significantly downregulated in NSCLC and serves as a potential diagnostic biomarker for the disease.