bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Paper-Based Documentation Practices in Medical Resuscitations to Inform the Design of Electronic Documentation Tools
Authors: Jagannath Swathi , Sarcevic Aleksandra , Multak Nina , Myers Sage
Published: December 2018

Objective

Despite growing use of electronic health records, many resuscitation settings still use paper-based documentation. The fast-paced and safety-critical nature of trauma and medical resuscitation environments pose challenges for real-time documentation. This study aims to understand paper-based documentation practices and inform the design of efficient electronic documentation solutions for supporting safety-critical medical processes.

Methods

Data were collected through in situ observations of nurse documenters during resuscitation events and postevent interviews with nurses. These data were analyzed using frequency distribution and qualitative, open-coding techniques. Data analysis focused on the following 3 main documentation factors: temporal distribution of documentation, total number of filled out sections on the paper flow sheet across all resuscitations, and completeness of documentation per resuscitation.

Results

Findings from this study highlight the time-critical nature of these settings, showing that 74% of the documentation was completed within the first 15 minutes of the resuscitation. Some sections of the paper flow sheet were filled out more than others, and a few sections were left incomplete across all events. Interviews with nurses provided insight about documentation experiences in a fast-paced environment, including variable usage of flow sheet based on nurse experience level and patient scenarios, supplemental documentation mechanisms, and information needs and preferences.

Conclusions

Several design implications are discussed to inform the design of effective electronic documentation systems. Design implications focus on layout structure, prepopulating items, section placement, and completion status of the flow sheet. Future plans for research focus on combining video review with in situ observations and conducting detailed interviews with nurses to better understand their documentation experiences and preferences.
Comparing the Evolution of Risk Culture in Radiation Oncology, Aviation, and Nuclear Power
Authors: Abdulla Ahmed , Schell Kristen R. , Schell Michael C.
Published: December 2018

Objectives

All organizations seek to minimize the risks that their operations pose to public safety. This task is especially significant if they deal with complex or hazardous technologies. Five decades of research in quantitative risk analysis have generated a set of risk management frameworks and practices that extend across a range of such domains. Here, we investigate the risk culture in three commercial enterprises that require exceedingly high standards of execution: radiation oncology, aviation, and nuclear power.

Methods

One of the characteristics of high reliability organizations is their willingness to learn from other such organizations. We investigate the extent to which this is true by compiling a database of the major publications on risk within each of the three fields. We conduct a bibliographic coupling analysis on the combined database to identify connections among publications. This analysis reveals the strength of engagement across disciplinary boundaries and the extent of cross-adoption of best practices.

Results

Our results show that radiation oncology is more insulated than the other two fields in its adoption and propagation of state-of-the-art risk management tools and frameworks that have transformed aviation and nuclear power into high reliability enterprises with actuarially low risk.

Conclusions

Aviation and nuclear power have established risk cultures that cross-pollinate. In both nature and extent, we found a distinct difference in radiation oncology's engagement with the risk community, and it lags behind the other two fields in implementing best practices that might mitigate or eliminate risks to patient safety.
Ascending Aortic Aneurysm Secondary to Isolated Noninfectious Ascending Aortitis
Authors: Cozijnsen Luc , ter Borg Evert-Jan , Braam Richard L. , Seldenrijk Cees A. , Heijmen Robin H. , Bouma Berto J. , Merkel Peter A.
Published: December 2018

Isolated noninfectious ascending aortitis (I-NIAA) is increasingly diagnosed at histopathologic review after resection of an ascending aortic aneurysm. PubMed was searched using the term aortitis; publications addressing the issue were reviewed, and reference lists of selected articles were also reviewed. Eleven major studies investigated the causes of an ascending aortic aneurysm or dissection requiring surgical repair: the prevalence of noninfectious aortitis ranged from 2% to 12%. Among 4 studies of lesions limited to the ascending aorta, 47% to 81% of cases with noninfectious aortitis were I-NIAA, more frequent than Takayasu arteritis or giant cell arteritis. Because of its subclinical nature and the lack of “syndromal signs” as in Takayasu arteritis or giant cell arteritis, I-NIAA is difficult to diagnose before complications occur, such as an aortic aneurysm or dissection. Therefore, surgical specimens of dissected aortic tissue should always be submitted for pathologic review. Diagnostic certainty requires the combination of a standardized histopathologic and clinical investigation. This review summarizes the current knowledge on I-NIAA, followed by a suggested approach to diagnosis, management, and follow-up. An illustrative case of an uncommon presentation is also presented. More follow-up studies on I-NIAA are needed, and diagnosis and follow-up of I-NIAA may benefit from the development of diagnostic biomarkers.
Bionics and green technology in maritime shipping: an assessment of the effect of Salvinia air-layer hull coatings for drag and fuel reduction
Authors: Busch J. , Barthlott W. , Brede M. , Terlau W. , Mail M.
Published: December 2018

To save energy and reduce environmental impacts, new technologies towards a development of a sustainable ‘greener’ economy are needed. The main opportunity to improve sustainability by reducing emissions is within the transport sector. More than 90% of all goods worldwide are transported by ships. Particularly maritime ships using heavy fuel oil and marine gas oil play a major role. The total fuel consumption of shipping in 2016 was about 250 m t (domestic ca. 50 m t, international shipping ca. 200 m t). The vast portion of the energy consumption of a ship is the need to overcome the drag between ship hull and water—depending on the shape of the vessel and its size up to 90% of total fuel consumption. This means reducing drag helps to save fuel and reduces carbon emissions as well as pollution considerably. Different techniques for drag reduction are known, e.g. the micro-bubble technique or the bulbous bow. We investigated a novel bioinspired technique since 2002: the application of biomimetic surfaces with long-term stable air layers on ship hulls, serving as a slip agent. This technology is based on the Salvinia Effect, allowing a permanent stabilization of air layers under water. In this case study, we analysed the possible savings, which also could be combined with modified micro-bubble technologies. We calculated, based on a selection of five ship types, representing 75% of the world fleet, that air-layer hull coatings could lead to estimated savings of 32.5 million tons of fuel (meaning 13.0% of the worldwide shipping fuel consumption), equal to 18.5 billion US$ and 130.0 million tons of CO
2e
per year. The positive impacts on global temperature and other greenhouse gases are calculated and could be a contributing factor in accomplishing the UN Sustainable Development Goals and the Paris Agreement to the UN Framework Convention on Climate Change. The study is a contribution to enhance our patchy knowledge concerning the potential economic and ecological benefit of bionics and biomimetic technologies.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia
Authors: Suárez Nicolás M. , Musonda Kunda G. , Escriva Eric , Njenga Margaret , Agbueze Anthony , Camiolo Salvatore , Davison Andrew J. , Gompels Ursula A.
Published: December 2018

Background

In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, in whom multiple-strain infection is linked to disease severity. The situation is less documente in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in HIV-positive women. We investigated HCMV strain diversity.

Methods

High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-positive and seven HIV-negative) at 4 or 16 weeks (or both) postpartum and analysed by genotyping 12 hypervariable HCMV genes.

Results

Among the 20 samples from 14 donors (13 HIV-positive and one HIV-negative) that yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to five strains per person were apparent in nine HIV-positive women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within the hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus-entry and immunomodulation, but not between genes more distant from each other.

Conclusions

Breast milk from HIV-positive women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.
Transcriptional Circuit Fragility Influences HIV Proviral Fate
Authors: Morton Emily L. , Forst Christian V. , Zheng Yue , De Paula-Silva Ana B. , Ramirez Nora-Guadalupe P. , Planelles Vicente , D’Orso Iván
Published: December 2018

Transcriptional circuit architectures can be evolutionarily selected to precisely dictate a given response. Unlike these cellular systems, HIV is regulated through a complex circuit composed of two successive phases (host and viral), which create a positive feedback loop facilitating viral replication. However, it has long remained unclear whether both phases operate identically and to what extent the host phase influences the entire circuit. Here we report that while the host phase is regulated by a checkpoint whereby KAP1 mediates transcription activation, the virus evolved a minimalist system bypassing KAP1. Given the complex circuit’s architecture, cell-to-cell KAP1 fluctuations impart heterogeneity in the host transcriptional responses thus affecting the feedback loop. Mathematical modeling of a complete circuit reveals how these oscillations ultimately influence homogeneous reactivation potential of a latent virus. Thus, while HIV drives molecular innovation to fuel robust gene activation, it experiences transcriptional fragility thereby influencing viral fate and cure efforts.

In Brief

HIV evolved a minimalist but robust transcriptional circuit bypassing host regulatory checkpoints; however, the fragility of the circuit in the host phase (which primes HIV for activation) largely affects proviral transcription and fate.

Highlights

The host and viral phases of the HIV transcriptional circuit have different functional requirements

HIV evolved a minimalist program to robustly bypass host cell regulatory checkpoints

A mathematical model reveals that the host phase is subject to transcriptional circuit fragility

Host transcriptional circuit fragility influences the viral feedback and latency reversal potential
Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback
Authors: Vila Charles-Henri , Williamson Ross S , Hancock Kenneth E , Polley Daniel B
Published: December 2018

Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Despite the anatomical weight of this connection, optogenetic activation of ACtx neurons produced only modest changes in the IC neuron firing rates. To determine whether different modes of cortical activation could more faithfully reveal the strength of feedforward connectivity, we employed a closed-loop evolutionary optimization procedure that tailored voltage command signals to the laser based on firing rate variations recorded from single units in the IC of awake male and female mice. Within minutes, the evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that suppressed or enhanced sound-evoked IC firing rate. These findings demonstrate that the feedforward influence between brain areas can vary both in sign and degree depending on how presynaptic neurons are activated in time.
The quagga mussel genome and the evolution of freshwater tolerance: Supplementary Material
Authors: Calcino Andrew D , de Oliveira Andre Luiz , Simakov Oleg , Schwaha Thomas , Zieger Elisabeth , Wollesen Tim , Wanninger Andreas
Published: December 2018

European freshwater dreissenid mussels evolved from marine ancestors during the Miocene approximately 30 million years ago and today include some of the most successful and destructive invasive invertebrate species of temperate freshwater environments. Here we sequenced the genome of the quagga mussel Dreissena rostriformis to identify evolutionary adaptations involved in embryonic osmoregulation. We found high gene expression levels of a novel subfamily of lophotrochozoan-specific aquaporin water channel, a vacuolar ATPase and a sodium/hydrogen exchanger during early cleavage, a period defined by the formation of intercellular fluid-filled 'cleavage cavities'. Independent expansions of the lophotrochoaquaporin clade that coincide with at least five independent colonisation events of freshwater environments confirm their central role in freshwater adaptation. The pattern of repeated aquaporin expansion and the evolution of membrane-bound fluid-filled osmoregulatory structures in diverse taxa points to a fundamental principle guiding the evolution of freshwater tolerance that may provide a framework for future efforts towards invasive species control.
Prior Perceptual-Cognitive Training Builds Mental Resistance During Acute Physical Fatigue In Professional Rugby Athletes
Authors: Faubert Jocelyn , Barthes Sylvain
Published: December 2018

Elite athletes are engaged in intensive physical training programs because it improves their physical strength and agility, but also to build endurance for resisting the negative impact of fatigue. Although it is well accepted that physical fitness can reduce the consequence of mental fatigue it is still unknown whether specific mental training can reduce the negative impact of physical fatigue on perceptual-cognitive functions. Here we show in professional rugby players that acute physical fatigue can dramatically reduce mental performance required for processing 3D-Multiple Object Tracking (3D-MOT) and that prior training, void of any physical demands, can build resistance to these detrimental effects.
Maternal Obesity Enhances Oocyte Chromosome Abnormalities Associated With Aging
Authors: Yun Yan , Wei Zijie , Hunter Neil
Published: December 2018

Obesity is increasing globally and maternal obesity has adverse effects on pregnancy outcomes and the long-term health of offspring. Maternal obesity has been associated with pregnancy failure through impaired oogenesis and embryogenesis. However, whether maternal obesity causes chromosome abnormalities in oocytes has remained unclear. Here we show that chromosome abnormalities are increased in the oocytes of obese mice and identify weakened sister-chromatid cohesion as the likely cause. Numbers of full-grown follicles retrieved from obese mice were the same as controls and the efficiency of in vitro oocyte maturation remained high. However, chromosome abnormalities presenting in both metaphase-I and metaphase-II were elevated, most prominently the premature separation of sister chromatids. Weakened sister-chromatid cohesion in oocytes from obese mice was manifested both as the terminalization of chiasmata in metaphase-I and as increased separation of sister centromeres in metaphase II. Obesity-associated abnormalities were elevated in older mice implying that maternal obesity exacerbates the deterioration of cohesion seen with advancing age.
A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells
Authors: Mboge Mam Y. , Chen Zhijuan , Khokhar Daniel , Wolff Alyssa , Ai Lingbao , Heldermon Coy D. , Bozdag Murat , Carta Fabrizio , Supuran Claudiu T. , Brown Kevin D. , McKenna Robert , Frost Christopher J. , Frost Susan C.
Published: December 2018

The most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX cooperates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple negative breast cancer (TNBC), appears to coordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+shuttle system in CA IX to facilitate proton efflux through MCT4.
Chronology of motor-mediated microtubule streaming
Authors: Ravichandran Arvind , Duman Özer , Hoore Masoud , Saggiarato Guglielmo , Vliegenthart Gerard A. , Auth Thorsten , Gompper Gerhard
Published: December 2018

We introduce a computer-based simulation model for coarse-grained, effective motor-mediated interaction between microtubule pairs to study the time-scales that compose cytoplasmic streaming. We characterise microtubule dynamics in two-dimensional systems by chronologically arranging five distinct processes of varying duration that make up streaming, from microtubule pairs to collective dynamics. The structures found were polarity sorted due to the propulsion of antialigned microtubules. This also gave rise to the formation of large polar-aligned domains, and streaming at the domain boundaries. Correlation functions, mean squared displacements, and velocity distributions reveal a cascade of processes ultimately leading to microtubule streaming and advection, spanning multiple microtubule lengths. The characteristic times for the processes span over three orders of magnitude from fast single-microtubule processes to slow collective processes. Our approach can be used to directly test the importance of molecular components, such as motors and crosslinking proteins between microtubules, on the collective dynamics at cellular scale.
Determining the link between alpha-gal-containing antigens in North American ticks and red meat allergy
Authors: Crispell Gary , Commins Scott P. , Archer-Hartman Stephanie A. , Choudhary Shailesh , Dharmarajan Guha , Azadi Parastoo , Karim Shahid
Published: December 2018

Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteome, carbohydrate analysis, and basophil activation approaches. Using anti-α-gal antibodies, α-gal was identified in the salivary glands of bothAm. americanumandIx. scapularis, whileAm. maculatumandDe. variabilisappeared to lack the sugar. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.Am. americanumticks were fed human blood (lacks α-gal) using an artificial membrane feeding system to determine the source of α-gal. N-linked glycan analysis revealed thatAm. americanumandIx. scapularishave α-gal in their saliva and salivary glands, butAm. maculatumcontains no detectable quantity. Salivary samples fromAm. americanumandIx. scapularisstimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, our data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
Latitudinal and seasonal variation in space use by a large, predatory reef fish,Plectropomus leopardus
Authors: Scott Molly E. , Heupel Michelle R. , Simpfendorfer Colin A. , Matley Jordan K. , Pratchett Morgan S.
Published: December 2018

Temperature directly affects the metabolic rate and resource requirements of ectothermic animals, which is likely to influence their movement and habitat use. Space use is a fundamental component of an animal’s ecology, and the extent of an animal’s home range has consequences for individual distributions, community structure and ecosystem function. As ocean temperatures continue to rise as a result of global warming, determining the effects of temperature on space use and movement patterns of important fisheries species is vital.

Our aim was to investigate the spatial and temporal variation in space use by a tropical fisheries species, the leopard coralgrouper (Plectropomus leopardus), from two latitudinally distinct locations on Australia’s Great Barrier Reef to determine the potential response of large‐bodied tropical fishes to ocean warming through behavioural modification.

Using passive acoustic telemetry of 36 tagged individuals, we found that both core use areas (50%KUD) and home range extent (95%KUD) varied with respect to location, season, body size and temperature. Average home range extent (95%KUD) for taggedP. leoparduswas 0.32 km2at the high‐latitude location (Heron Island) compared to 0.23 km2at the low‐latitude location (Opal Reef). However, core use areas (50%KUD) did not differ significantly between the two locations.

Seasonal differences were also apparent at both locations withP. leopardusshowing contraction in home range extent during the summertime. This effect was most pronounced at the low‐latitude location where home range was significantly reduced during summer when temperatures exceeded 27°C.

Taken together, our findings indicate that higher ambient temperature may elicit a sustained and significant decline in space use by a commercially important reef fish. Given projected increases in ocean temperature due to global climate change, large‐bodied reef fishes may be increasingly constrained in their movement and space use, which will have ramifications for individual fitness, population viability, fisheries productivity and ecological function.

Aplain language summaryis available for this article.
Corticosteroid therapy in drug‐induced liver injury: Pros and cons
Authors: Hu Ping Fang , Xie Wei Fen
Published: December 2018

Drug‐induced liver injury (DILI) is a liver toxicity induced by a drug or its metabolite. The incidence of DILI continues to increase and it has been an enormous challenge worldwide, while the prognosis is not optimistic. Currently, the most effective treatment for DILI is to suspend the offending drug(s) and to avoid re‐exposure, with no definitive therapy available for idiosyncratic DILI with or without acute liver failure. Given the anti‐inflammatory effects of corticosteroids, they have been widely used in DILI in clinical practice, although their efficacy remains controversial. Several studies have shown their beneficial effects but a few reports have refuted the efficacy of corticosteroids in treating patients with DILI. In this review, we summarized the history and current status of corticosteroid use in liver diseases and the pros and cons of corticosteroid treatment in DILI, and we explored the DILI candidates who may benefit from corticosteroid therapy, the administration route and dosage, and the adverse effects related to corticosteroid use.
Inefficiency of manual weeding in rainfed rice systems affected by parasitic weeds
Authors: N'cho Simon Akahoua , Mourits Monique , Rodenburg Jonne , Oude Lansink Alfons
Published: December 2018

Manual weeding is the predominant weed control practice and the most labor‐consuming activity in smallholder, rainfed rice systems in sub‐Saharan Africa. This study investigates the technical inefficiency of weeding labor, other labor, and overall inputs, and identifies sources of technical inefficiency of weeding labor in the context of parasitic weed infestation. The analysis applies a two‐stage approach. First, a directional input distance function DEA approach was used to compute input‐specific technical inefficiencies. Second, sources of technical inefficiency of weeding labor were identified using a truncated bootstrap regression. Data from 406 randomly selected smallholder farmers from Benin (n = 215) and Côte d'Ivoire (n = 191) were used. The technical inefficiency of weeding labor was high in both countries (58% in Côte d'Ivoire and 69% in Benin). This implies that a substantial fraction of weeding labor could be saved without reducing rice productivity or increasing the use of other inputs. A decrease in the technical inefficiency of weeding labor with an increase in production scale was observed. In addition, weeding regime and education level were each associated to significant changes in the technical inefficiency of weeding labor.
Novel 3D in vitro models to evaluate trophoblast migration and invasion
Authors: You Yuan , Stelzl Patrick , Zhang Yonghong , Porter James , Liu Hong , Liao Ai‐Hua , Aldo Paulomi B. , Mor Gil
Published: December 2018

Problem

Embryo implantation depends on the interactions between the developing embryo and the maternal endometrium. Signals originating from the decidua play a critical role in the process of implantation and trophoblast invasion; however, the molecular mechanisms mediating this interaction are poorly understood. The objective of this study was to develop in vitro models that would mimic the processes of attachment, migration, and early invasion of the trophoblast.

Methods of study

First trimester trophoblast cells (Sw.71 cells) were cultured in low attachment plates to form blastocyst‐like spheroids (BLS). Epithelial‐mesenchymal transition (EMT) characterization during BLS formation was determined by RT‐PCR and Western Blot. The two 3D in vitro culture models consist of (a) trophoblast migration: BLS cultured in suspension (b) trophoblast invasion: human endometrium stromal cells (HESC) plated in the bottom of a 96‐well plate, covered by Matrigel and BLS transferred on top. Matrigel was used to mimic the human endometrial extracellular matrix.

Results

Using 3D cell culture systems and real‐time imaging, we are able to determine the impact of endometrial factors on trophoblast cell function. Endometrial stromal cells promote blastocyst‐like spheroid migration of trophoblast cells and invasion of the extracellular matrix.

Conclusion

We report the characterization of 3D in vitro models to evaluate the interaction between endometrial cells and trophoblast during the process of migration and invasion. The models are useful tools in order to further study the molecular mechanism of embryo‐maternal uterine cells interactions.
Effect of preoperative detrusor underactivity on long‐term surgical outcomes of photovaporization and holmium laser enucleation in men with benign prostatic hyperplasia: a lesson from 5‐year serial follow‐up data
Authors: Cho Min Chul , Yoo Sangjun , Park Juhyun , Cho Sung Yong , Son Hwancheol , Oh Seung‐June , Paick Jae‐Seung
Published: December 2018

Objectives

To investigate the impact of preoperative detrusor underactivity (DU) on serial treatment outcomes over the course of 5 years after photovaporization (PV) or holmium laser enucleation (HoLEP) in patients with benign prostatic hyperplasia (BPH), to compare its impact after PV vs HoLEP, and to identify predictors of long‐term lower urinary tract symptoms (LUTS) improvement.

Materials and Methods

This study involved 245 patients with BPH who had complete 5‐year follow‐up data (PV using 120W‐HPS, n = 143, HoLEP, n = 102), grouped as follows: PV‐HPS‐DU(+), n = 114; PV‐HPS‐DU(−), n = 29; HoLEP‐DU(+), n = 56; and HoLEP‐DU(−), n = 46. Bladder contractility index (BCI) < 100 was regarded as DU. Serial treatment outcomes for the International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry and serum PSA level at 6 months, and at 1, 2, 3, 4 and 5 years after surgery, were compared among the groups. LUTS improvement was defined as a reduction in total IPSS of ≥50% relative to baseline.

Results

Improvement in total IPSS, quality of life (QoL) index and post‐void residual urine volume (PVR) in the PV‐HPS‐DU(+) and PV‐HPS‐DU(−) groups were maintained up to 5 years after PV, except for maximum urinary flow rate (Qmax) and bladder voiding efficiency. In the HoLEP‐DU(+) and HoLEP‐DU(−) groups, improvements in all outcome variables were maintained up to 5 years after HoLEP. Deteriorations in subtotal voiding symptom score, total IPSS and Qmax with time during the long‐term period after surgery were more pronounced in the PV‐HPS‐DU(+) and HoLEP‐DU(+) groups than in the PV‐HPS‐DU(−) and HoLEP‐DU(−) groups. Reductions in subtotal voiding symptom score, total IPSS, QoL index, and serum PSA were greater in the HoLEP‐DU(+) group than in the PV‐HPS‐DU(+) group throughout follow‐up. The type of surgery (HoLEP vs PV) and higher baseline BCI were independent predictors of LUTS improvement at 5 years after surgery.

Conclusion

Generally, improvement of micturition symptoms, QoL and PVR in patients with DU appears to be maintained up to 5 years after PV or HoLEP. Deterioration of voiding symptoms and urinary flow rate at long‐term follow‐up visits after PV or HoLEP was more pronounced in patients with LUTS/BPH with DU than in those without DU. Patients with BPH with DU may benefit from more complete removal of prostatic adenoma by HoLEP and greater baseline bladder contractility in terms of micturition symptoms and QoL.
Degeneration of dopaminergic circuitry influences depressive symptoms in Lewy body disorders
Authors: Patterson Lina , Rushton Steven P. , Attems Johannes , Thomas Alan J. , Morris Christopher M.
Published: December 2018

Abstract

Aims

Depression is commonly observed even in prodromal stages of Lewy body disorders (LBD), and is associated with cognitive impairment and a faster rate of cognitive decline. Given the role of dopamine in the development of movement disorders, but also in motivation and reward, we investigated neurodegenerative pathology in dopaminergic circuitry in Parkinson's disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) patients in relation to depressive symptoms.

Methods

α‐synuclein, hyperphosphorylated tau and amyloid‐beta pathology was assessed in 17 DLB, 14 PDD and 8 PD cases within striatal and midbrain subregions, with neuronal cell density assessed in substantia nigra and ventral tegmental area. Additionally, we used a structural equation modeling (SEM) approach to investigate the extent to which brain connectivity might influence the deposition of pathological proteins within dopaminergic pathways.

Results

A significantly higher α‐synuclein burden was observed in the substantia nigra (P = 0.006), ventral tegmental area (P = 0.011) and nucleus accumbens (P = 0.031) in LBD patients with depression. Significant negative correlations were observed between cell density in substantia nigra with Lewy body (LB) Braak stage (P = 0.013), whereas cell density in ventral tegmental area showed negative correlations with LB Braak stage (P = 0.026) and neurofibrillary tangle Braak stage (P = 0.007).

Conclusions

Dopaminergic α‐synuclein pathology appears to drive depression. Selective targeting of dopaminergic pathways may therefore provide symptomatic relief for depressive symptoms in LBD patients.
Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations
Authors: Miyauchi Eisaku , Matsuda Tatsuo , Kiyotani Kazuma , Low Siew‐Kee , Hsu Yu‐Wen , Tsukita Yoko , Ichinose Masakazu , Sakurada Akira , Okada Yoshinori , Saito Ryoko , Nakamura Yusuke
Published: December 2018

Recent clinical trials of non‐small cell lung cancer with immune checkpoint inhibitors revealed that patients with epidermal growth factor receptor (EGFR) mutations had more unfavorable outcomes compared with those with wild‐type EGFR. However, the underlying mechanism for the link between EGFR mutations and immune resistance remains unclear. We performed T cell receptor (TCR) repertoire analysis of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate the characteristics of TCR repertoires. We collected a total of 39 paired (normal and tumor) lung tissue samples (20 had EGFR mutations) and conducted TCR repertoire analysis as well as whole‐exome sequencing (WES) and transcriptome analysis. The TCR diversity index in EGFR‐mutant tumors was significantly higher than that in EGFR‐wild‐type tumors (median [range] 552 [162‐1,135] vs 230 [30‐764]; P < .01), suggesting higher T cell clonal expansion in EGFR‐wild‐type tumors than in EGFR‐mutant tumors. In WES, EGFR‐mutant tumors showed lower numbers of non‐synonymous mutations and predicted neoantigens than EGFR‐wild‐type tumors (P < .01, P = .03, respectively). The number of non‐synonymous mutations revealed a positive correlation with the sum of frequencies of the TCRβ clonotypes of 1% or higher in tumors (r = .52, P = .04). The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR‐mutant and wild‐type lung tumors. Our findings provide important information for understanding the molecular mechanism behind EGFR‐mutant patients showing unfavorable responses to immune checkpoint inhibitors.
Noteworthy effect of slight variation in aliphatic chain length of trisubstituted imidazole inhibitors against epidermal growth factor receptor L858R/T790M/C797S mutant in cancer therapy
Authors: Akher Farideh Badichi , Farrokhzadeh Abdolkarim , Soliman Mahmoud E. S.
Published: December 2018

11h is a very potent inhibitor against epidermal growth factor receptor triple mutation L858R/T790M/C797S (EGFRTM) with 13‐fold stronger potency than the FDA‐approved osimertinib. Recently, two new EGFRTM inhibitors, 11d and 11e, were reported which revealed 2.8‐ and 2.3‐fold stronger potency than 11h, respectively. 11h, 11d, and 11e have the same structures but differ only in their aliphatic chain length. However, the exact effects of differential aliphatic chain length on the inhibitory potencies of these compounds require further elaboration at the atomistic level, hence the objective of this report. Various computational tools were employed for this purpose. From our findings, it was revealed that van der Waals (vdW) interactions modulate the binding mechanisms of these inhibitors and play the most important role in the differential inhibitory activities of 11d, 11h, and 11e. The strong hydrogen bond formation between the aliphatic chain of 11d and key residue ARG841 was recognized as the reason for its higher activity and inhibitory potency relative to 11h and 11e. Moreover, the extension of the N‐terminal loop into the active site for vdW interaction with the phenyl group of 11e and carbon–hydrogen bond formed between the aliphatic chain of 11e and LEU718 engendered a higher activity of 11e than 11h.
SAR study on inhibitors of GIIA secreted phospholipase A2 using machine learning methods
Authors: Zhang Shengde , Li Yang , Qin Zijian , Tu Guipin , Chen Guang , Yan Aixia
Published: December 2018

GIIA secreted phospholipase A2 (GIIA sPLA2) is a potent target for drug discovery. To distinguish the activity level of the inhibitors of GIIA sPLA2, we built 24 classification models by three machine learning algorithms including support vector machine (SVM), decision tree (DT), and random forest (RF) based on 452 compounds. The molecules were represented by CORINA descriptors, MACCS fingerprints, and ECFP4 fingerprints, respectively. The dataset was split into a training set containing 312 compounds and a test set containing 140 compounds by Kohonen's self‐organizing map (SOM) strategy and a random strategy. A recursive feature elimination (RFE) method and an information gain (IG) method were used in the selection of molecular descriptors. Three favorable performing models were obtained. They were built by SVM algorithm with CORINA descriptors (Models 1A and 2A) and ECFP4 fingerprints (Model 10A). In the prediction of test set of Model 10A, the accuracy reached 90.71%, and the Matthews correlation coefficient (MCC) values reached 0.82. In addition, the 452 inhibitors were clustered into eight subsets by K‐Means algorithm for analyzing their structural features. It was found that highly active inhibitors mainly contained indole scaffold or indolizine scaffold and four side chains.
Peptide and protein mimetics by retro and retroinverso analogs
Authors: Rai Jagdish
Published: December 2018

Retroinverso analog of a natural polypeptide can sometimes mimic the structure and function of the natural peptide. The additional advantage of using retroinverso analog is that it is resistant to proteolysis. The retroinverso analogs have peptide sequence in reverse direction with respect to natural peptide and also have chirality of amino acid inverted from L to D. The D amino acids cannot be recognized by common proteases of the body; therefore, these peptides will not be degraded easily and have a longer‐lasting effect as vaccine and inhibitor drugs. There have been many contested propositions about the geometric relationship between a peptide and its retro, inverso, or retroinverso analog. A retroinverso analog sometimes fails to adopt the structure that can mimic the function of the natural peptide. In such cases, partial retroinverso analog and other modifications can help in achieving the desired structure and function. Here, we review the theory, major experimental attempts, prediction methods, and alternative strategies related to retroinverso peptidomimetics.
Immunotherapies based on PD-1/PD-L1 pathway inhibitors in ovarian cancer treatment
Authors: Pawłowska A , Suszczyk D , Okła K , Barczyński B , Kotarski J , Wertel I
Published: December 2018

Immunotherapies based on anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway inhibitors may turn out effective in ovarian cancer (OC) treatment. They can be used in combination with standard therapy and are especially promising in recurrent and platinum-resistant OC. There is growing evidence that the mechanism of the PD-1/PD-L1 pathway can be specific for a particular histological cancer type. Interestingly, the data have shown that the PD-1/PD-L1 pathway blockade may be effective, especially in the endometrioid type of OC. It is important to identify the cause of anti-tumor immune response suppression and exclude its other mechanisms in OC patients. It is also necessary to conduct subsequent studies to confirm in which OC cases the treatment is effective and how to select patients and combine drugs to improve patient survival.
Sparse, Inconsistent and Unreliable: Tax Records and the World Inequality Report 2018
Authors: Galbraith James K.
Published: December 2018

This article reviews the World Inequality Report 2018, a large collaborative data project based on the work of Thomas Piketty and the late Anthony Atkinson, which critiques the entire literature of inequality measurement from survey data and purports to provide superior, unprecedented and reliable coverage of income and wealth inequalities over the entire world, based primarily on tax records. The article examines three major issues: the coverage provided by tax data in the world economy, the consistency of tax data with other sources of information on income inequality, and the peculiarities of tax‐based measurement of inequality in the United States. Then a comparison is made with measures drawn from other forms of administrative data — specifically payroll records — which are generally more consistent with records of inequality measured in household surveys than are tax records. Following this, the article discusses the analysis of wealth and wealth inequality before offering a few closing remarks about policy.
Bilingual toddlers’ comprehension of mixed sentences is asymmetrical across their two languages
Authors: Potter Christine E. , Fourakis Eva , Morin‐Lessard Elizabeth , Byers‐Heinlein Krista , Lew‐Williams Casey
Published: December 2018

In bilingual language environments, infants and toddlers listen to two separate languages during the same key years that monolingual children listen to just one and bilinguals rarely learn each of their two languages at the same rate. Learning to understand language requires them to cope with challenges not found in monolingual input, notably the use of two languages within the same utterance (e.g., Do you like the perro? or ¿Te gusta el doggy?). For bilinguals of all ages, switching between two languages can reduce the efficiency in real‐time language processing. But language switching is a dynamic phenomenon in bilingual environments, presenting the young learner with many junctures where comprehension can be derailed or even supported. In this study, we tested 20 Spanish–English bilingual toddlers (18‐ to 30‐months) who varied substantially in language dominance. Toddlers’ eye movements were monitored as they looked at familiar objects and listened to single‐language and mixed‐language sentences in both of their languages. We found asymmetrical switch costs when toddlers were tested in their dominant versus non‐dominant language, and critically, they benefited from hearing nouns produced in their dominant language, independent of switching. While bilingualism does present unique challenges, our results suggest a united picture of early monolingual and bilingual learning. Just like monolinguals, experience shapes bilingual toddlers’ word knowledge, and with more robust representations, toddlers are better able to recognize words in diverse sentences.
Interspecific and intraspecific variation in diet preference in five Atlantic forest dung beetle species
Authors: Raine Elizabeth H. , Mikich Sandra B. , Lewis Owen T. , Slade Eleanor M.
Published: December 2018

1. Dung beetles are commonly assumed to be generalist feeders, but there has been limited work in identifying whether there is interspecific variation in feeding preference. Equally, there has been no work exploring whether generalist feeding behaviour in a species is a result of within‐species specialisation.

2. This study identified the individual and species‐level feeding preferences of five dung beetle species towards human, jaguar and pig dung using a choice experiment.

3. It was found that species varied in their preference for the dung types, but there was no evidence that within a species, individual beetles varied in their dung choice. These findings were similar to results from field experiments that are more typically used to assess feeding preferences in dung beetles.

4. The results suggest that individual specialism in feeding may not be common in dung beetles. However, there is variation in feeding preferences among species, which is often overlooked and can have implications for the ecosystem functions they provide. It is suggested that choice arenas can be used to assess feeding preferences in dung beetle species that are not abundant enough to reliably estimate dietary choice from field studies.
Evaluation of the effectiveness of the presentation of virtual histology slides by students during classes. Are there any differences in approach between dentistry and general medicine students?
Authors: Tauber Zdenek , Cizkova Katerina , Lichnovska Radka , Lacey Helena , Erdosova Bela , Zizka Radovan , Kamarad Vojtech
Published: December 2018

Introduction

Virtual microscopy, used as a method to teach histology, has many undeniable advantages. However, the usefulness of this method is somewhat limited by the difficulties students face in finding their way through huge amounts of digital data, compounded by decreased interaction between students and teachers. We describe the results of a recent pilot project which combined the modern teaching methods of active learning, where students themselves present histological slides and make use of the virtual microscopy system.

Methods

Students’ responses to a structured questionnaire and examination results were evaluated.

Results

We found that a combination of both electronic materials and textbooks was commonly used by students to prepare for practical teaching sessions, with electronic resources being used regularly by the majority of students. No statistically relevant differences were found between the approaches of dentistry vs general medicine students. Cooperation between students’ groups during the preparation for individual presentations was seen to be beneficial by a majority of dentistry students; they reported that the introduction of student‐led presentations improved their quality of preparation for practical lessons, as well as increasing their participation and activity level in the lessons themselves. These different approaches and motivations between students of dentistry and general medicine are reflected in the test results where dentistry students are more successful.

Conclusion

We confirm that there are differences in motivation, approaches and examination results between both groups of students, which should be taken into account and which could lead to differentiation of future curricula for both study courses.