bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of serial coronary computed tomography angiography in the evaluation of coronary plaque progression
Authors: Dahal Suraj , Budoff Matthew J. 
Published: October 2019

Purpose of review
The purpose is to review the use of coronary computed tomography (CT) angiography to assess coronary plaque burden/progression and to discuss about recent clinical trials that have utilized this imaging modality to study the effect of new pharmacotherapies on plaque burden/progression.

Recent findings
There are numerous clinical trials that have utilized coronary CT angiography to demonstrate the potential benefits of statins, apixaban, rivaroxaban, aged garlic extract, biologic agents, and omega-3 fatty acids to reduce coronary plaque progression. Coronary CT angiography can identify high-risk plaques and can also quantify total plaque burden, both of which are independent risk factors to predict major adverse cardiac events.

Summary
Coronary heart disease remains one of the leading cause of mortality in the world. Utilizing coronary CT angiography, it is possible to identify rupture-prone plaques and also to quantify the total plaque burden. New pharmacotherapies that have the potential to reduce plaque progression have been used in clinical trials and these trials have utilized coronary CT angiography to track coronary atheroma progression. In future, we will see frequent utilization of coronary CT angiography to track coronary atheroma.
Ethanol Intoxication of Young Children
Authors: Gaw Christopher E. , Osterhoudt Kevin C. 
Published: October 2019

Abstract
Ethanol intoxication of infants and young children can be a challenging diagnosis in the pediatric emergency department, and features of the poisoning may differ in comparison with adolescents. The sources of ethanol exposures in this age are varied and include unintentional, malicious, and iatrogenic etiologies. Young children exposed to ethanol often present with mixed clinical signs and symptoms that may not fit the traditional ethanol or sedative-hypnotic toxidrome. Pediatric ethanol intoxications are often managed supportively, and recovery is usually rapid. The purpose of this review is to describe the sources of ethanol poisoning among children 6 years and younger, highlight presenting symptoms and pharmacokinetic considerations unique to this age group, and review management strategies. In addition, published cases of ethanol poisoning due to ingestion among young infants are compiled for presentation.
SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis
Authors: Wu Robin T. , Timberlake Andrew T. , Abraham Paul F. , Gabrick Kyle S. , Lu Xiaona , Peck Connor J. , Sawh-Martinez Rajendra F. , Steinbacher Derek M. , Alperovich Michael A. , Persing John A. 
Published: October 2019

Background:
De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.

Methods:
Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).

Results:
Twenty-eight patients participated: 10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.

Conclusions:
This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Definition of Immunological Nonresponse to Antiretroviral Therapy: A Systematic Review
Authors: Rb-Silva Rita , Goios Ana , Kelly Christine , Teixeira Pedro , João Cristina , Horta Ana , Correia-Neves Margarida 
Published: October 2019

Background:
Terms and criteria to classify people living with HIV on antiretroviral therapy who fail to achieve satisfactory CD4+ T-cell counts are heterogeneous, and need revision and summarization.

Methods:
We performed a systematic review of PubMed original research articles containing a set of predefined terms, published in English between January 2009 and September 2018. The search retrieved initially 1360 studies, of which 103 were eligible. The representative terminology and criteria were extracted and analyzed.

Results:
Twenty-two terms and 73 criteria to define the condition were identified. The most frequent term was “immunological nonresponders” and the most frequent criterion was “CD4+ T-cell count <350 cells/µL after ≥24 months of virologic suppression.” Most criteria use CD4+ T-cell counts as a surrogate, either as an absolute value before antiretroviral therapy initiation or as a change after a defined period of time. Distinct values and time points were used. Only 9 of the 73 criteria were used by more than one independent research team. Herein we propose 2 criteria that could help to reach a consensus.

Conclusions:
The high disparity in terms and criteria here reported precludes data aggregation and progression of the knowledge on this condition, because it renders impossible to compare data from different studies. This review will foster the discussion of terms and criteria to achieve a consensual definition.
System Factors Affecting Patient Safety in the OR
Authors: Adams-McGavin Robert Chris , Jung James J. , van Dalen Anne S. H. M. , Grantcharov Teodor P. , Schijven Marlies P. 
Published: October 2019

Objective:
The objective of this study is to determine the characteristics and frequency of intraoperative safety threats and resilience supports using a human factors measurement tool.

Background:
Human factors analysis can provide insight into how system elements contribute to intraoperative adverse events. Empiric evidence on safety threats and resilience in surgical practice is lacking.

Methods:
A cross-sectional study of 24 patients undergoing elective laparoscopic general surgery at a single center in the Netherlands from May to November, 2017 was conducted. Video, audio, and patient physiologic data from all included procedures were obtained through a multichannel synchronized recording device. Trained analysts reviewed the recordings and coded safety threats and resilience supports. The codes were categorized into 1 of 6 categories (person, task, tools and technology, physical environment, organization, and external environment).

Results:
A median of 14 safety threats [interquartile range (IQR) 11–16] and 12 resilience supports (IQR 11–16) were identified per case. Most safety threat codes (median 9, IQR 7–12) and resilience support codes (median 10, IQR 7–12) were classified in the person category. The organization category contained a median of 2 (IQR 1–2) safety threat codes and 2 (IQR 2–3) resilience support codes per case. The tools and technology category contributed a small number of safety threats (median 1 per case, IQR 0–1), but rarely provided resilience support.

Conclusions:
Through a detailed human factors analysis of elective laparoscopic general surgery cases, this study provided a quantitative analysis of the existing safety threats and resilience supports in a modern endoscopic operating room.
Transparent and Reproducible Research Practices in the Surgical Literature
Authors: Hughes Taylor , Niemann Andrew , Tritz Daniel , Boyer Kryston , Robbins Hal , Vassar Matt 
Published: October 2019

AbstractPrevious studies have established a baseline of minimal reproducibility in the social science and biomedical literature. Clinical research is especially deficient in factors of reproducibility. Surgical journals contain fewer clinical trials than non-surgical ones, suggesting that it should be easier to reproduce the outcomes of surgical literature. In this study, we evaluated a broad range of indicators related to transparency and reproducibility in a random sample of 300 articles published in surgery-related journals between 2014 and 2018. A minority of our sample made available their materials (2/186, 95% C.I. 0–2.2%), protocols (1/196, 0–1.3%), data (19/196, 6.3–13%), or analysis scripts (0/196, 0–1.9%). Only one study was adequately pre-registered. No studies were explicit replications of previous literature. Most studies (162/292 50–61%) declined to provide a funding statement, and few declared conflicts of interest (22/292, 4.8–11%). Most have not been cited by systematic reviews (183/216, 81–89%) or meta-analyses (188/216, 83–91%), and most were behind a paywall (187/292, 58–70%). The transparency of surgical literature could improve with adherence to baseline standards of reproducibility.
Structural and mechanical remodeling of the cytoskeleton maintains tensional homeostasis in 3D microtissues under acute dynamic stretch
Authors: Walker Matthew , Rizzuto Pauline , Godin Michel , Pelling Andrew E. 
Published: October 2019

AbstractWhen stretched, cells cultured on 2D substrates share a universal softening and fluidization response that arises from poorly understood remodeling of well-conserved cytoskeletal elements. It is known, however, that the structure and distribution of the cytoskeleton is profoundly influenced by the dimensionality of a cell’s environment. Therefore, in this study we aimed to determine whether cells cultured in a 3D matrix share this softening behavior and to link it to cytoskeletal remodeling. To achieve this, we developed a high-throughput approach to measure the dynamic mechanical properties of cells and allow for sub-cellular imaging within physiologically relevant 3D microtissues. We found that fibroblast, smooth muscle and skeletal muscle microtissues strain softened but did not fluidize, and upon loading cessation, they regained their initial mechanical properties. Furthermore, microtissue prestress decreased with the strain amplitude to maintain a constant mean tension. This adaptation under an auxotonic condition resulted in lengthening. A filamentous actin cytoskeleton was required, and responses were mirrored by changes to actin remodeling rates and visual evidence of stretch-induced actin depolymerization. Our new approach for assessing cell mechanics has linked behaviors seen in 2D cultures to a 3D matrix, and connected remodeling of the cytoskeleton to homeostatic mechanical regulation of tissues.
Automated highly multiplexed super-resolution imaging of protein nano-architecture in cells and tissues
Authors: Klevanski Maja , Herrmannsdoerfer Frank , Venkataramani Varun , Sass Steffen , Heilemann Mike , Kuner Thomas 
Published: October 2019

ABSTRACTUnderstanding the nano-architecture of protein machines in diverse sub-cellular compartments remains a challenge despite rapid progress in super-resolution microscopy. While singlemolecule localization microscopy techniques allow the visualization and identification of cellular structures with near-molecular resolution, multiplex-labeling of tens of target proteins within the same sample has not yet been achieved routinely. However, single sample multiplexing is essential to detect patterns that threaten to get lost in multi-sample averaging. Here, we report maS3TORM (multiplexed automated serial staining stochastic optical reconstruction microscopy), a microscopy approach capable of fully automated 3D dSTORM imaging and solution exchange employing a re-staining protocol to achieve highly multiplexed protein localization within individual biological samples. We demonstrate 3D super-resolution images of 15 target proteins in single cultured cells and 16 targets in individual neuronal tissue samples with <10 nm localization precision. This allowed us to define novel nano-architectural features of protein distribution within the presynaptic nerve terminal.
Parallel and non-parallel changes of the gut microbiota during trophic diversification in repeated young adaptive radiations of sympatric cichlid fish
Authors: Härer Andreas , Torres-Dowdall Julián , Rometsch Sina , Yohannes Elizabeth , Machado-Schiaffino Gonzalo , Meyer Axel 
Published: October 2019

AbstractRecent increases in understanding the ecological and evolutionary roles of microbial communities has underscored their importance for their hosts’ biology. Yet, little is known about gut microbiota dynamics during early stages of ecological diversification and speciation. We studied the gut microbiota of extremely young adaptive radiations of Nicaraguan crater lake cichlid fish (Amphilophus cf. citrinellus) to test the hypothesis that parallel evolution in trophic ecology is associated with parallel changes of the gut microbiota. Bacterial communities of the water (eDNA) and guts were highly distinct, indicating that the gut microbiota is shaped by host-specific factors. Across individuals of the same crater lake, differentiation in trophic ecology was associated with gut microbiota differentiation, suggesting that diet affects the gut microbiota. However, differences in trophic ecology were much more pronounced across than within species whereas little evidence was found for similar patterns in taxonomic and functional changes of the gut microbiota. Across the two crater lakes, we could not detect evidence for parallel changes of the gut microbiota associated with trophic ecology. Similar cases of non-parallelism have been observed in other recently diverged fish species and might be explained by a lack of clearly differentiated niches during early stages of ecological diversification.
Perceptual learning evidence for an interval- and modality-invariant representation of subsecond time
Authors: Xiong Ying-Zi , Guan Shu-Chen , Yu Cong 
Published: October 2019

AbstractA central theme in time perception research is whether subsecond timing relies on a dedicated centralized clock, or on distributed neural temporal dynamics. A fundamental constraint is the interval- and modality-specificity in perceptual learning of temporal interval discrimination (TID), which argues against a dedicated centralized clock, but is more consistent with multiple distributed mechanisms. Here we demonstrated an abstract, interval- and modality-invariant, representation of subsecond time in the brain. Participants practiced TID at a specific interval (100 ms), and received exposure to a transfer interval (200 ms), or to a different auditory/visual modality, through training of an orthogonal task. This double training enabled complete transfer of TID learning to the untrained interval, and mutual complete transfer between visual and auditory modalities. These results demonstrate an interval- and modality-invariant representation of subsecond time, which resembles a centralized clock, on top of the known distributed timing mechanisms and their readout and integration.
Ingested insecticide to control Aedes aegypti: Developing a novel dried attractive toxic sugar bait device for intra-domiciliary control
Authors: Sippy Rachel , Rivera Galo E. , Sanchez Valeria , Heras Froilán Heras , Morejón Bianca , Ayala Efraín Beltrán , Hikida Robert S. , López-Latorre María A. , Aguirre Alex , Stewart-Ibarra Anna M. , Larsen David A. , Neira Marco 
Published: October 2019

AbstractBackgroundIllnesses transmitted by Aedes aegypti (Linnaeus, 1762) such as dengue, chikungunya and Zika comprise a considerable global burden; mosquito control is the primary public health tool to reduce disease transmission. Current interventions are inadequate and insecticide resistance threatens the effectiveness of these options. Dried attractive bait stations (DABS) are a novel mechanism to deliver insecticide to Ae. aegypti. The DABS are a high-contrast 28 inch2 surface coated with dried sugar-boric acid solution. Ae. aegypti are attracted to DABS by visual cues only, and the dried sugar solution elicits an ingestion response from Ae. aegypti landing on the surface. The study presents the development of the DABS and tests of their impact on Ae. aegypti mortality in the laboratory and a series of semi-field trials.MethodsWe conducted multiple series of laboratory and semi-field trials to assess the survivability of Ae. aegypti mosquitoes exposed to the DABS. For laboratory experiments we assessed the lethality, the killing mechanism, and the shelf life of the device through controlled experiments. In the semi-field trials, we released laboratory-reared female Ae. aegypti into experimental houses typical of peri-urban tropical communities in South America in three trial series with six replicates each. Laboratory experiments were conducted in Quito, Ecuador, and semi-field experiments were conducted in Machala, Ecuador – an area with abundant wild populations of Ae. aegypti and endemic arboviral transmission.ResultsIn the laboratory, complete lethality was observed after 48 hours regardless of physiological status of the mosquito. The killing mechanism was determined to be through ingestion, as the boric acid disrupted the gut of the mosquito. In experimental houses, total mosquito mortality was greater in the treatment house for all series of experiments (p<0.0001).ConclusionsThe DABS devices were effective at killing female Ae. aegypti under a variety of laboratory and semi-field conditions. DABS are a promising intervention for interdomiciliary control of Ae. aegypti and arboviral disease prevention.
The majority of the matrix protein TapA is dispensable for biofilm formation byBacillus subtilis
Authors: Earl Chris , Arnaouteli Sofia , Sukhodub Tetyana , MacPhee Cait E. , Stanley-Wall Nicola R. 
Published: October 2019

SummaryBiofilm formation is a co-operative behaviour where microbial cells become embedded in an extracellular matrix. This biomolecular matrix plays a key role in the manifestation of the beneficial or detrimental outcome mediated by the collective of cells.Bacillus subtilisis an important bacterium for understanding the general principles of biofilm formation and is a plant growth-promoting organism. The protein components of theB. subtilismatrix include the secreted proteins BslA, which forms a hydrophobic coat over the biofilm, and TasA, which forms protease-resistant fibres needed for structuring. A third protein TapA (forTasAanchoring and assemblyprotein) is needed for biofilm formation and helps TasA fibre formationin vivobut is dispensable for TasA-fibre assemblyin vitro. Here we show that TapA is subjected to proteolytic cleavage in the biofilm and that only the first 57 amino acids of the 253-amino acid protein are required for biofilm architecture. However, through the construction of a strain which lacks all eight extracellular proteases, we show that proteolytic cleavage by these enzymes is not a prerequisite for TapA function. It remains unknown why TapA is synthesized at a full length of 253 amino acids when the first 57 are sufficient for biofilm structuring, but the findings do not exclude the core conserved region of TapA having a second role beyond that of structuring theB. subtilisbiofilm.
Stable and dynamic representations of value in the prefrontal cortex
Authors: Enel Pierre , Wallis Joni , Rich Erin 
Published: October 2019

AbstractThe ability to associate positive and negative outcomes with predictive stimuli allows us to make optimal decisions. These stimulus-value associations are kept up to date by comparing an expected value with the experienced outcome. When a stimulus and its outcome are separated by a delay, the value associated with the stimulus must be held in mind for such comparisons to be possible, however little is known about the neural mechanisms that hold value representations online across delays. Temporarily remembering task-relevant information has been extensively studied in the context of item-specific working memory, and different hypotheses have suggested this ability requires either persistent or transient neuronal activity, with stable or dynamic representations respectively. To test these different hypotheses in the context of value representations, we recorded the spiking activity of neurons in the orbitofrontal and anterior cingulate cortex of two monkeys performing a task in which visual cues predicted a reward delivered after a short delay. We found that features of all hypotheses were simultaneously present in prefrontal activity and therefore no single hypothesis was exclusively supported. Instead, we report mixed dynamics that support robust, time invariant value representations while also encoding the information in a temporally specific manner. We suggest that this hybrid coding is important for optimal behavior and might be a critical mechanism supporting flexible cognitive abilities.
A Machine Learning Approach to Predict Hypotensive Events in ICU Settings
Authors: Moghadam Mina Chookhachizadeh , Masoumi Ehsan , Bagherzadeh Nader , Ramsingh Davinder , Li Guann-Pyng , Kain Zeev N 
Published: October 2019

AbstractPurposePredicting hypotension well in advance provides physicians with enough time to respond with proper therapeutic measures. However, the real-time prediction of hypotension with high positive predictive value (PPV) is a challenge due to the dynamic changes in patients’ physiological status under the drug administration which is limiting the amount of useful data available for the algorithm.MethodsTo mimic real-time monitoring, we developed a machine learning algorithm that uses most of the available data points from patients’ record to train and test the algorithm. The algorithm predicts hypotension up to 30 minutes in advance based on only 5 minutes of patient’s physiological history. A novel evaluation method is proposed to assess the algorithm performance as a function of time at every timestamp within 30 minutes prior to hypotension. This evaluation approach provides statistical tools to find the best possible prediction window.ResultsDuring 181,000 minutes of monitoring of about 400 patients, the algorithm demonstrated 94% accuracy, 85% sensitivity and 96% specificity in predicting hypotension within 30 minutes of the events. A high PPV of 81% obtained and the algorithm predicted 80% of the events 25 minutes prior to their onsets. It was shown that choosing a classification threshold that maximizes the F1 score during the training phase contributes to a high PPV and sensitivity.ConclusionThis study reveals the promising potential of the machine learning algorithms in real-time prediction of hypotensive events in ICU setting based on short-term physiological history.