bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Extended Pedicled Transverse Rectus Abdominis Myocutaneous Flap for Extensive Chest Wall Defect Reconstruction After Mastectomy for Locally Advanced Breast Cancer
Authors: Lin Yun-Nan , Ou-Yang Fu , Hsieh Meng-Chien , Lee Su-Shin , Huang Shu-Hung , Chuang Chieh-Han , Chang Chih-Hau , Kuo Yur-Ren , Hou Ming-Feng , Lin Sin-Daw
Published: December 2019

Background

The reconstruction of a large postmastectomy chest wall defect for patients with stage III/IV breast cancer is a challenge for plastic surgeons. In this study, we present the application of an extended transverse rectus abdominis myocutaneous (TRAM) flap to easily and safely reconstruct these defects.

Patients and Methods

A retrospective review from November 1997 to November 2016 revealed that 65 patients with stage III/IV breast cancer immediately underwent postmastectomy TRAM flap reconstruction. In total, 16 patients were enrolled in this study based on the inclusion criteria of a postmastectomy chest skin defect size of greater than or equal to 100 cm2 and a TRAM flap size of greater than or equal to 80% of the lower abdominal area for reconstruction.

Results

Eleven (68.9%) and 5 patients (31.3%) were diagnosed with stage III and stage IV breast cancer, respectively. The chest wall skin defects ranged from 135 to 440 cm2. All flap areas exceeded 80% of the lower abdominal area. Overall, 100% of the harvested flaps were used in 3 patients, and only 1 patient had marginal necrosis in zone IV. No total flap loss was observed. The average length of hospital stay was 5.8 days, and the mean follow-up duration was 46.6 months (range, 4.5–117.7 months). On a Likert scale, the mean follow-up satisfaction score of 10 patients was 4.7.

Conclusions

Even when the flap area exceeded 80% of the lower abdominal area, the extended TRAM flap proved an effective and viable method for the immediate reconstruction of extensive postmastectomy chest wall skin defects, resulting in few minor complications and high follow-up satisfaction scores.
Nonoperative Treatment Versus Appendectomy for Acute Nonperforated Appendicitis in Children
Authors: Patkova Barbora , Svenningsson Anna , Almström Markus , Eaton Simon , Wester Tomas , Svensson Jan F.
Published: December 2019

Objective:

The aim of this study was to evaluate the safety and feasibility of nonoperative treatment of acute nonperforated appendicitis in children during 5 years of follow-up.

Methods:

A 4-year follow-up of a previous randomized controlled pilot trial, including 50 children with acute nonperforated appendicitis, was performed. The patients were initially randomized to nonoperative treatment with antibiotics or appendectomy with 1-year follow-up previously reported. Data were extracted from the computerized notes and telephone interviews.

The primary outcome was treatment failure, defined as need for a secondary intervention under general anesthesia, related to the previous diagnosis of acute nonperforated appendicitis.

Results:

The children were followed up for at least 5 years [median 5.3 (range 5.0–5.6)] after inclusion. There were no failures in the appendectomy group (0/26) and 11 failures in the nonoperative group (11/24). Nine failures had occurred during the first year after inclusion, 2 of whom had histologically confirmed appendicitis. There were 2 further patients with recurrent acute appendicitis 1 to 5 years after inclusion. Both these patients had uncomplicated laparoscopic appendectomies for histologically confirmed acute appendicitis. There were no losses to follow-up.

Conclusions:

At 5 years of follow-up 46% of children treated with antibiotics for acute nonperforated appendicitis had undergone an appendectomy, although acute appendicitis was only histologically confirmed in 4/24 (17%). Treatment with antibiotics seems to be safe in the intermediate-term; none of the children previously treated nonoperatively re-presented with complicated appendicitis.
Esophageal Adenocarcinoma After Antireflux Surgery in a Cohort Study From the 5 Nordic Countries
Authors: Maret-Ouda John , Santoni Giola , Wahlin Karl , Artama Miia , Brusselaers Nele , Färkkilä Martti , Lynge Elsebeth , Mattsson Fredrik , Pukkala Eero , Romundstad Pål , Tryggvadóttir Laufey , von Euler-Chelpin My , Lagergren Jesper
Published: December 2019

Objective:

We aimed to clarify the long-term risk development of EAC after antireflux surgery.

Summary of Background Data:

Gastroesophageal reflux disease (GERD) increases EAC risk, but whether antireflux surgery prevents EAC is uncertain.

Methods:

Multinational, population-based cohort study including individuals with GERD from all 5 Nordic countries in 1964–2014. First, EAC risk after antireflux surgery in the cohort was compared with the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs, compared EAC risk in GERD patients with antireflux surgery with those with nonsurgical treatment.

Results:

Among 942,071 GERD patients, 48,863 underwent surgery and 893,208 did not. Compared to the corresponding background population, EAC risk did not decrease after antireflux surgery [SIR 4.90 (95% CI 3.62–6.47) 1–<5 years and SIR 4.57 (95% CI 3.44–5.95) ≥15 years after surgery]. Similarly, no decrease was found for patients with severe GERD (esophagitis or Barrett esophagus) after surgery [SIR 6.09 (95% CI 4.39–8.23) 1–<5 years and SIR = 5.27 (95% CI 3.73–7.23) ≥15 years]. The HRs of EAC were stable comparing the surgery group with the nonsurgery group with GERD [HR 1.71 (95% CI 1.26–2.33) 1–<5 years and HR 1.69 (95% CI 1.24–2.30) ≥15 years after treatment], or for severe GERD [HR 1.56 (95% CI 1.11–2.20) 1–<5 years and HR 1.57 (95% CI 1.08–2.26) ≥15 years after treatment].

Conclusions:

Surgical treatment of GERD does not seem to reduce EAC risk.
Differential Effect of Demographics, Processing Speed, and Depression on Cognitive Function in 755 Non-demented Community-dwelling Elderly Individuals
Authors: Mougias Antonios , Christidi Foteini , Synetou Margarita , Kotrotsou Irene , Valkimadi Polena , Politis Antonios
Published: December 2019

Background:

Several factors may account for inter- and intra-individual variability in cognitive functions, including age, gender, education level, information processing speed, and mood.

Objective:

To evaluate the combined contribution of demographic factors, information processing speed, and depressive symptoms to scores on several diagnostic cognitive measures that are commonly used in geriatric neuropsychological practice in Greece.

Methods:

Using a cross-sectional study, we established a multivariate general linear model and analyzed the predictive role of age, gender, education, information processing speed (Trail Making Test—Part A), and depressive symptoms (Geriatric Depression Scale—15 Items) on measures of general cognitive status (Mini-Mental State Examination), verbal memory (Rey Auditory Verbal Learning Test), language (Confrontation Naming), and executive functions (Category and Phonemic Fluency, Trail Making Test—Part B) for a sample of 755 healthy, community-dwelling Greek individuals aged 50 to 90 years.

Results:

Participant factors significantly but differentially contributed to cognitive measures. Demographic factors and information processing speed emerged as the significant predictors for the majority of the cognitive measures (Mini-Mental State Examination; Rey Auditory Verbal Learning Test; Confrontation Naming; Category and Phonemic Fluency; Trail Making Test—Part B), whereas depressive symptoms significantly predicted verbal memory and semantic fluency measures (Rey Auditory Verbal Learning Test and Category Fluency).

Conclusions:

Clinicians should consider participant demographics, underlying slowing of processing speed, and depressive symptoms as potential confounding factors in cognitive measures. Our findings may explain the observed inter- and intra-individual variability in cognitive functions in the elderly population.
Pure Alexia: A Combined First-Person Account and Neuropsychological Investigation
Authors: Hansen Klaus , Starrfelt Randi
Published: December 2019

Pure alexia is an acquired reading disorder where patients’ ability to read words and text is severely impaired, while their writing is left unaffected. Patients with pure alexia typically recover some reading ability over time, although most never regain their premorbid reading skills. A few studies have reported some behavioral and imaging correlates of such remission; however, little is known about the patients’ experience of their reading impairment. This paper contains a first-person account of pure alexia, describing the first author’s (K.H.) experience of his remission from severe reading problems immediately following a posterior cerebral artery stroke to the mild pure alexia characterizing his reading ability today. To provide a context for this account, we also present neuropsychological and reading data obtained from K.H. at several time points during his recovery.
Validation and Clinical Experience With a Turkish Language Version of the Pittman Ostomy Complication and Severity Index
Authors: Sayar Serap , Vural Fatma
Published: December 2019

PURPOSE:

The purpose of this study was to evaluate the content validity and interrater reliability of a Turkish language version of the Pittman Ostomy Complication and Severity Index (OCSI).

DESIGN:

Psychometric evaluation of instrument.

SUBJECTS AND SETTING:

The sample comprised 90 individuals living with an ostomy for 2 to 6 months. Their mean age was 59.48 years (SD 13.292); 52.2% were female. Almost two-thirds (73.3%, n = 66) had experienced at least 1 ostomy complication. The study was conducted in the Wound and Stoma Therapy Unit of the Dokuz Eylül University Hospital General Surgery Clinic and Polyclinic in Izmir, Turkey.

METHODS:

A Turkish language version of the OCSI was created using a translation, back-translation technique. The instrument's content validity was analyzed by 26 experts. Interrater reliability test was evaluated using Cohen's κ and intraclass correlation coefficients. Data were collected between January 15, 2017 and July 30, 2017 through face-to-face interviews conducted in our Wound and Stoma Therapy Unit.

RESULTS:

The overall content validity index was 0.95. Cohen's κ coefficient varied from 0.70 and 1.0 for all items. The Pearson correlation coefficient and intraclass correlation coefficient were 0.982 (P = .000) and 0.986 (P = .000), respectively, indicating good internal consistency. The most prevalent complications were leakage (41.1%), peristomal moisture-associated skin damage (42.2%), and stomal retraction (27.7%).

CONCLUSIONS:

Findings indicate that the Turkish language version of the Pittman OCSI is a reliable and valid instrument for assessment of presence and severity of early postoperative complications in individuals with an ostomy. We found the instrument parsimonious, easy-to-use, and clinically practical. It can be used to determine appropriate interventions to prevent or treat complications and evaluate the effects of nursing interventions designed to improve outcomes for patients with ostomies.
Dogs perceive and spontaneously normalize formant-related speaker and vowel differences in human speech sounds
Authors: Root-Gutteridge Holly , Ratcliffe Victoria F. , Korzeniowska Anna T. , Reby David
Published: December 2019

Domesticated animals have been shown to recognize basic phonemic information from human speech sounds and to recognize familiar speakers from their voices. However, whether animals can spontaneously identify words across unfamiliar speakers (speaker normalization) or spontaneously discriminate between unfamiliar speakers across words remains to be investigated. Here, we assessed these abilities in domestic dogs using the habituation–dishabituation paradigm. We found that while dogs habituated to the presentation of a series of different short words from the same unfamiliar speaker, they significantly dishabituated to the presentation of a novel word from a new speaker of the same gender. This suggests that dogs spontaneously categorized the initial speaker across different words. Conversely, dogs who habituated to the same short word produced by different speakers of the same gender significantly dishabituated to a novel word, suggesting that they had spontaneously categorized the word across different speakers. Our results indicate that the ability to spontaneously recognize both the same phonemes across different speakers, and cues to identity across speech utterances from unfamiliar speakers, is present in domestic dogs and thus not a uniquely human trait.
Inquiline predator increases nutrient-cycling efficiency of
Nepenthes rafflesiana
pitchers
Authors: Lam Weng Ngai , Chou Ying Yi , Leong Felicia Wei Shan , Tan Hugh Tiang Wah
Published: December 2019

The modified-leaf pitchers of
Nepenthes rafflesiana
pitcher plants are aquatic, allochthonous ecosystems that are inhabited by specialist inquilines and sustained by the input of invertebrate prey. Detritivorous inquilines are known to increase the nutrient-cycling efficiency (NCE) of pitchers but it is unclear whether predatory inquilines that prey on these detritivores decrease the NCE of pitchers by reducing detritivore populations or increase the NCE of pitchers by processing nutrients that may otherwise be locked up in detritivore biomass.
Nepenthosyrphus
is a small and poorly studied genus of hoverflies and the larvae of one such species is a facultatively detritivorous predator that inhabits the pitchers of
N. rafflesiana
. We fitted a consumer–resource model to experimental data collected from this system. Simulations showed that systems containing the predator at equilibrium almost always had higher NCEs than those containing only prey (detritivore) species. We showed using a combination of simulated predator/prey exclusions that the processing of the resource through multiple pathways and trophic levels in this system is more efficient than that accomplished through fewer pathways and trophic levels. Our results thus support the vertical diversity hypothesis, which predicts that greater diversity across trophic levels results in greater ecosystem functioning.
Erwin Louis Hahn. 9 June 1921—20 September 2016
Authors: Pines Alexander , Budker Dmitry
Published: December 2019

Erwin Louis Hahn was one of the most innovative physical scientists in recent history, impacting generations of scientists through his work in nuclear magnetic resonance (NMR), optics, and the intersection of these two fields. Starting with his discovery of the spin echo, a phenomenon of monumental significance and practical importance, Hahn launched a revolution in how we think about spin physics, with numerous implications following in many other areas of science. Current students of NMR and coherent optics quickly discover that many of the key concepts and techniques in these fields derive directly from his work.
A design principle of root length distribution of plants
Authors: Jung Yeonsu , Park Keunhwan , Jensen Kaare H. , Kim Wonjung , Kim Ho-Young
Published: December 2019

Shaping a plant root into an ideal structure for water capture is increasingly important for sustainable agriculture in the era of global climate change. Although the current genetic engineering of crops favours deep-reaching roots, here we show that nature has apparently adopted a different strategy of shaping roots. We construct a mathematical model for optimal root length distribution by considering that plants seek maximal water uptake at the metabolic expenses of root growth. Our theory finds a logarithmic decrease of root length density with depth to be most beneficial for efficient water uptake, which is supported by biological data as well as our experiments using root-mimicking network systems. Our study provides a tool to gauge the relative performance of root networks in transgenic plants engineered to endure a water deficit. Moreover, we lay a fundamental framework for mechanical understanding and design of water-absorptive growing networks, such as medical and industrial fluid transport systems and soft robots, which grow in porous media including soils and biotissues.
Lignin biosynthesis: old roads revisited and new roads explored
Authors: Dixon Richard A. , Barros Jaime
Published: December 2019

Lignin is a major component of secondarily thickened plant cell walls and is considered to be the second most abundant biopolymer on the planet. At one point believed to be the product of a highly controlled polymerization procedure involving just three potential monomeric components (monolignols), it is becoming increasingly clear that the composition of lignin is quite flexible. Furthermore, the biosynthetic pathways to the major monolignols also appear to exhibit flexibility, particularly as regards the early reactions leading to the formation of caffeic acid from coumaric acid. The operation of parallel pathways to caffeic acid occurring at the level of shikimate esters or free acids may help provide robustness to the pathway under different physiological conditions. Several features of the pathway also appear to link monolignol biosynthesis to both generation and detoxification of hydrogen peroxide, one of the oxidants responsible for creating monolignol radicals for polymerization in the apoplast. Monolignol transport to the apoplast is not well understood. It may involve passive diffusion, although this may be targeted to sites of lignin initiation/polymerization by ordered complexes of both biosynthetic enzymes on the cytosolic side of the plasma membrane and structural anchoring of proteins for monolignol oxidation and polymerization on the apoplastic side. We present several hypothetical models to illustrate these ideas and stimulate further research. These are based primarily on studies in model systems, which may or may not reflect the major lignification process in forest trees.
Deep learning for bridge load capacity estimation in post-disaster and -conflict zones
Authors: Pamuncak Arya , Guo Weisi , Soliman Khaled Ahmed , Laory Irwanda
Published: December 2019

Many post-disaster and post-conflict regions do not have sufficient data on their transportation infrastructure assets, hindering both mobility and reconstruction. In particular, as the number of ageing and deteriorating bridges increases, it is necessary to quantify their load characteristics in order to inform maintenance and asset databases. The load carrying capacity and the design load are considered as the main aspects of any civil structures. Human examination can be costly and slow when expertise is lacking in challenging scenarios. In this paper, we propose to employ deep learning as a method to estimate the load carrying capacity from crowdsourced images. A convolutional neural network architecture is trained on data from over 6000 bridges, which will benefit future research and applications. We observe significant variations in the dataset (e.g. class interval, image completion, image colour) and quantify their impact on the prediction accuracy, precision, recall and
F
1 score. Finally, practical optimization is performed by converting multiclass classification into binary classification to achieve a promising field use performance.
Experimental study on the compressive strength, damping and interfacial transition zone properties of modified recycled aggregate concrete
Authors: Lei Bin , Liu Huajian , Yao Zhimin , Tang Zhuo
Published: December 2019

At present, many modification methods have been proposed to improve the performance of recycled aggregate concrete (RAC). In this study, tests on the compressive strength and damping properties of modified RAC with the addition of different proportions of recycled coarse aggregate (RCA) (0, 50, 100%), rubber powder (10, 15, 20%), steel fibre (5, 7.5, 10%) and fly ash (15, 20, 5%) are carried out. To elucidate the effect of the modification method on the interfacial transition zone (ITZ) performance of RAC, model ITZ specimens are used for push-out tests. The results show that when the replacement rate of RCA reaches 100%, the loss factor of the RAC is 6.0% higher than that of natural aggregate concrete; however, the compressive strength of the RAC decreases by 22.6%. With the addition of 20% rubber powder, the damping capacity of the modified RAC increases by 213.7%, while the compressive strength of the modified RAC decreases by 47.5%. However, with the addition of steel fibre and fly ash, both the compressive strength and loss factor of the RAC specimens increase. With a steel fibre content of 10 wt%, the compressive strength and loss factor of the RAC increase by 21.9% and 15.2%, respectively. With a fly ash content of 25 wt%, the compressive strength and loss factor of the RAC increase by 8.6% and 6.9%, respectively. This demonstrates that steel fibre and fly ash are effective in improving both the damping properties and compressive strength of RAC, and steel fibre is more effective than fly ash. Two methods were used for modification of the RAC: reinforcing the RCA through impregnation with a 0.5% polyvinyl alcohol (PVA) emulsion and nano-SiO
2
solution, and strengthening the RAC integrally through the addition of fly ash as an admixture. Both of these techniques can improve the ITZ bond strength between the RAC and new mortar. Replacing 10% of the cement with fly ash in the new mortar is shown to be the best method to improve the ITZ strength.
Investigation of growth kinetics and partial denitrification performance in strain
Acinetobacter johnsonii
under different environmental conditions
Authors: Zhang Yang , Wang Xiujie , Wang Weiqi , Sun Zhitao , Li Jun
Published: December 2019

A denitrifying strain ZY04 with a high nitrite-accumulating rate was isolated and purified from activated sludge in a laboratory-scale A
2
/O reactor. The strain was characterized and identified as
Acinetobacter johnsonii
by 16S rDNA phylogenetic analysis. The sequences of the key functional genes (
napA
,
nirB
,
nirD
) involved in partial denitrification were amplified via polymerase chain reaction, which provided a basis for exploring gene expression. The effects of different environmental factors (C/N ratio, pH and temperature) on the partial denitrification performance and transcriptional levels of the functional genes during the logarithmic growth phase were investigated by batch experiments. The results showed that the partial denitrification performance was optimal when the C/N ratio was 5, the pH value was 6–8 and the temperature was 25°C. The gene expression during the logarithmic growth phase indicated the good performance of partial denitrification under different environmental conditions. All three functional genes exhibited the highest expression levels at 25°C. The results of inhibitory kinetics analysis revealed that three biokinetic models (Aiba, Edwards and Andrews) simulated the growth pattern of strain ZY04 inhibited by a single substrate (nitrate or sodium acetate) well. In the double-substrate inhibitory model, five models of nine combinations successfully fitted the growth characteristics of the strain affected by the double substrate of nitrate and sodium acetate. The relevant semi-saturation parameters and substrate inhibition parameters were obtained, and the correlation coefficient (
R
2
) reached 98%.
Characterization of interface properties of fluids by evaporation of a capillary bridge
Authors: Tadrist Loïc , Motte L. , Rahli O. , Tadrist Lourès
Published: December 2019

The surface properties between two non-miscible fluids are key elements to understand mass transfer, chemistry and bio-chemistry at interfaces. In this paper, surface properties are investigated in evaporating and non-evaporating conditions. A capillary bridge between two large plates (similar to a Hele-Shaw cell) is considered. The temporal evolution of surface forces and mass transfers due to evaporation of the liquid are measured. The force depends on surface properties of the substrate. It is adhesive in the wetting case and repulsive in the non-wetting case. The force is also shown to depend linearly on the volume of the capillary bridge
F
∝
V
0
and inversely to the height of the bridge. Modelling is performed to characterize both surface force and evaporation properties of the capillary bridge. The evaporation is shown to be diffusion driven and is decoupled from the bridge mechanics.
Conditions for the existence of isolated backbone curves
Authors: Hong Dongxiao , Hill Thomas L. , Neild Simon A.
Published: December 2019

Isolated backbone curves represent significant dynamic responses of nonlinear systems; however, as they are disconnected from the primary responses, they are challenging to predict and compute. To explore the conditions for the existence of isolated backbone curves, a generalized two-mode system, which is representative of two extensively studied examples, is used. A symmetric two-mass oscillator is initially studied and, as has been previously observed, this exhibits a perfect bifurcation between its backbone curves. As this symmetry is broken, the bifurcation splits to form an isolated backbone curve. Here, it is demonstrated that this perfect bifurcation, indicative of a symmetric structure, may be preserved when the symmetry is broken under certain conditions; these are derived analytically. With the symmetry broken, the second example—a single-mode nonlinear structure with a nonlinear tuned mass damper—is considered. The evolution of the system's backbone curves is investigated in nonlinear parameter space. It is found that this space can be divided into several regions, within which the backbone curves share similar topological features, defining the conditions for the existence of isolated backbone curves. This allows these features to be more easily accounted for, or eliminated, when designing nonlinear systems.
Parallel changes in gut microbiome composition and function during colonization, local adaptation and ecological speciation
Authors: Rennison Diana J. , Rudman Seth M. , Schluter Dolph
Published: December 2019

The processes of local adaptation and ecological speciation are often strongly shaped by biotic interactions such as competition and predation. One of the strongest lines of evidence that biotic interactions drive evolution comes from the repeated divergence of lineages in association with repeated changes in the community of interacting species. Yet relatively little is known about the repeatability of changes in gut microbial communities and their role in adaptation and divergence of host populations in nature. Here we use three cases of rapid, parallel adaptation and speciation in freshwater threespine stickleback to test for parallel changes in associated gut microbiomes. We find that features of the gut microbial communities have shifted repeatedly in the same direction in association with parallel divergence and speciation of stickleback hosts. These results suggest that changes to gut microbiomes can occur rapidly and predictably in conjunction with host evolution, and that host–microbe interactions might play an important role in host adaptation and diversification.
Right phenotype, wrong place: predator-induced plasticity is costly in a mismatched environment
Authors: Innes-Gold Anne A. , Zuczek Nicholas Y. , Touchon Justin C.
Published: December 2019

Like many animals, tadpoles often produce different, predator-specific phenotypes when exposed to risk of predation. It is generally assumed that such plasticity enhances survival in the presence of the predator and is costly elsewhere, but evidence remains surprisingly scarce. We measured (1) the survival trade-off of opposing phenotypes developed byDendropsophus ebraccatustadpoles when exposed to different predators and (2) which specific aspects of morphology drive any potential survival benefit or cost. Tadpoles developed predator-specific phenotypes after being reared with caged fish or dragonfly predators for two weeks. In 24 h predation trials with either a fish or a dragonfly, survival was highest in the groups with their matched predator, and lowest among with those the mismatched predator, with predator-naive controls being relatively intermediate. Then, using a large group of phenotypically variable predator-naive tadpoles, we found that increased survival rates are directly related to the morphological changes that are induced by each predator. This demonstrates that induced phenotypes are indeed adaptive and the product of natural selection. Furthermore, our data provide clear evidence of an environmental cost for phenotypic plasticity in a heterogeneous environment. Such costs are fundamental for understanding the evolution and maintenance of inducible phenotypes.
Antibiotic resilience: a necessary concept to complement antibiotic resistance?
Authors: Carvalho Gabriel , Forestier Christiane , Mathias Jean-Denis
Published: December 2019

Resilience is the capacity of systems to recover their initial state or functions after a disturbance. The concepts of resilience and resistance are complementary in ecology and both represent different aspects of the stability of ecosystems. However, antibiotic resilience is not used in clinical bacteriology whereas antibiotic resistance is a recognized major problem. To join the fields of ecology and clinical bacteriology, we first review the resilience concept from ecology, socio-ecological systems and microbiology where it is widely developed. We then review resilience-related concepts in microbiology, including bacterial tolerance and persistence, phenotypic heterogeneity and collective tolerance and resistance. We discuss how antibiotic resilience could be defined and argue that the use of this concept largely relies on its experimental measure and its clinical relevance. We review indicators in microbiology which could be used to reflect antibiotic resilience and used as valuable indicators to anticipate the capacity of bacteria to recover from antibiotic treatments.
Flexivirga caeni sp. nov., isolated from activated sludge
Authors: Keum Dong-ho , Lee Yong-jae , Lee Soon-youl , Im Wan-Taek
Published: December 2019

A Gram-stain-positive, strictly aerobic, non-motile, non-spore-forming and oval-shaped bacterium, designated strain BO-16T was isolated from activated sludge. In this study, we describe the taxonomic characterization and classification of this bacterium by using the polyphasic approach. Growth of BO-16T was observed at 10–40 °C (optimum, 25–37 °C) and at pH 5.0–10.0 (optimum, pH 7.0) on R2A agar. The major fatty acids it contained were iso-C16:0, anteiso-C17:0 and iso-C17 : 0 and the major polar lipids were diphosphatidylglycerol, phosphatidylinositol and phosphatidylethanolamine. This isoprenoid quinones included MK-8 (H4) and MK-8 (H6). The peptidoglycan contained lysine, serine, alanine, glycine and glutamic acid and represented the peptidoglycan type A4α. On the basis of 16S rRNA gene sequence similarity, BO-16T was shown to represent a member of the genus

Flexivirga

and to be related to

Flexivirga oryzae

KACC 18597T (98.4 % sequence similarity),

Flexivirga endophytica

KCTC 39536T (97.5 %),

Flexivirga alba

DSM 24460T (97.4 %) and

Flexivirga lutea

KCTC 39625T (97.3 %). The G+C content of the genomic DNA was 68.0 mol%. The DNA–DNA relatedness values between BO-16T and its closest phylogenetic neighbours were much lower than 70 %. BO-16T could be differentiated phylogenetically and phenotypically from the species of the genus

Flexivirga

﻿with validly published names. Therefore the isolate represents a novel species, for which the name Flexivirga caeni sp. nov. is proposed, with the type strain BO-16T (=KACC 19647T=LMG 30859T)
Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy female volunteers are associated with reduced negative bias and the gut bacterial composition
Authors: Johnstone Nicola , Milesi Chiara , Burn Olivia , van den Bogert Bartholomeus , Nauta Arjen , Hart Kathryn , Sowden Paul , Burnet Philip WJ , Kadosh Kathrin Cohen
Published: December 2019

Current research implicates pre- and probiotic supplementation as potential mediators for improving symptomology in numerous physical and emotional ailments. The alteration of emotional states via nutrient intake is an attractive concept for clinicians and consumers alike and may be an efficient channel to improved well-being. Here we focus on the period of late adolescence, which is a time of emotional refinement via maturation that significantly influences emotional, social and physical well-being in later years. Effective interventions such as nutritional supplementation in this age group have the potential to offset health-related costs in later life. In this study we examined multiple indices of mood and well-being in 64 healthy females in late adolescence in a 4-week double blind, placebo controlled Galacto-oligosaccharide (GOS) prebiotic supplement intervention. We also obtained stool samples at baseline and follow-up for microbiome sequencing and analyses. We found effects of the GOS intervention on sub-clinical self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may be influential in improving indices of pre-clinical anxiety.
Linkage of a plasma zinc signature and impaired insulin receptor activation: Implications for the mechanism of type 2 diabetes mellitus
Authors: Prabhakar Shashidhar M.
Published: December 2019

Type 2 diabetes mellitus (T2DM) is characterized by decreased plasma zinc levels and hyperzincuria, yet the underlying cause of these zinc disturbances is unknown. In this study, we compared postprandial plasma zinc levels in samples from T2DM and healthy control subjects to determine whether zinc is associated with a different set of proteins. We found that in T2DM a considerable amount of zinc remained following albumin/Ig depletion. A discrepancy in total amount of zinc in the remaining set of zinc-associated proteins identified and estimated by protein analysis as alpha-2 macroglobulin (A2M), and in T2DM alone some bacterial proteinases as well, indicated that the likely source of this discrepancy was from bacterial zinc proteinases trapped by A2M that obscured the high levels of these proteinases. Furthermore, an insulin receptor assay examined whether activated A2M (A2MFF) affected insulin receptor activation. The results showed a significant decrease in insulin receptor activation following repeated treatments with A2MFF but not after a single treatment with A2MFF. Our findings suggest that in T2DM, A2MFF likely arises from the trapping of zinc-dependent bacterial proteinases and impairs insulin receptor activation from a prolonged presence, which may result in a “receptor-protective” effect manifested as insulin resistance.
The CDK8 inhibitor DCA promotes a tolerogenic chemical immunophenotype in CD4+ T cells via a novel CDK8-GATA3-FOXP3 pathway
Authors: Arnett Azlann , Moo Keagan G , Flynn Kaitlin J , Sundberg Thomas B , Johannessen Liv , Shamji Alykhan F , Gray Nathanael S , Decker Thomas , Zheng Ye , Gersuk Vivian H , Levy David E , Marié Isabelle J , Rahman Ziaur S , Linsley Peter S , Xavier Ramnik J , Khor Bernard
Published: December 2019

Immune health requires innate and adaptive immune cells to engage precisely balanced pro- and anti-inflammatory forces. We employ the concept of chemical immunophenotypes to classify small molecules functionally or mechanistically according to their patterns of effects on primary innate and adaptive immune cells. The high-specificity, low-toxicity cyclin dependent kinase 8 (CDK8) inhibitor DCA exerts a distinct tolerogenic profile in both innate and adaptive immune cells. DCA promotes Treg and Th2 differentiation, while inhibiting Th1 and Th17 differentiation, in both murine and human cells. This unique chemical immunophenotype led to mechanistic studies showing that DCA promotes Treg differentiation in part by regulating a previously undescribed CDK8-GATA3-FOXP3 pathway that regulates early pathways of Foxp3 expression. These results highlight previously unappreciated links between Treg and Th2 differentiation and extend our understanding of the transcription factors that regulate Treg differentiation and their temporal sequencing. These findings have significant implications for future mechanistic and translational studies of CDK8 and CDK8 inhibitors.
Improving source modeling of auditory steady-state responses with frequency-specific brain maps
Authors: Farahani Ehsan Darestani , Wouters Jan , van Wieringen Astrid
Published: December 2019

Auditory steady-state responses (ASSRs) are evoked brain responses to modulated or repetitive acoustic stimuli. Due to a wide range of clinical and research applications, there is a great (clinical) interest to investigate the underlying neural generators of ASSRs. The cortical sources of ASSRs mostly are located in the auditory cortex (AC), although some studies avoiding prior assumptions regarding the number and location of the sources have also reported activity of sources outside of the AC. However, little is known about the number and location of these sources. In this study, we present a novel extension to minimum-norm imaging (MNI) which facilitates ASSR source reconstruction and provides a comprehensive and consistent picture of sources in response to low- as well as high modulation frequencies, monaurally presented to the left and right ears.

Results demonstrate that the proposed MNI approach is successful in reconstructing sources located both within (primary) and outside (non-primary) of the AC. The locations of the non-primary sources are consistent with the literature. Primary sources are detected in every experimental condition, thereby corroborating the robustness of the approach. Moreover, we show that the MNI approach is capable of reconstructing the subcortical activities of ASSRs. In summary, the results indicate that the MNI approach outperforms the previously used method of group-ICA, in terms of detection of sources in the AC, reconstructing the subcortical activities and reducing computational load.
Mining Archive.org’s Twitter Stream Grab for Pharmacovigilance Research Gold
Authors: Tekumalla Ramya , Asl Javad Rafiei , Banda Juan M.
Published: December 2019

In the last few years Twitter has become an important resource for the identification of Adverse Drug Reactions (ADRs), monitoring flu trends, and other pharmacovigilance and general research applications. Most researchers spend their time crawling Twitter, buying expensive pre-mined datasets, or tediously and slowly building datasets using the limited Twitter API. However, there are a large number of datasets that are publicly available to researchers which are underutilized or unused. In this work, we demonstrate how we mined over 9.4 billion Tweets from archive.org’s Twitter stream grab using a drug-term dictionary and plenty of computing power. Knowing that not everything that shines is gold, we used pre-existing drug-related datasets to build machine learning models to filter our findings for relevance. In this work we present our methodology and the 3,346,758 identified tweets for public use in future research.
CD42b immunostaining as a marker for placental fibrinoid in normal pregnancy and complications
Authors: Zhang Peilin
Published: December 2019

Background

There are two types of the fibrinoid deposits within the placenta, and the nature of these fibrinoid are poorly understood in clinical setting.

Design

Fibrinoid deposits within normal pregnancy and the pregnancy related complications are studied using the routine hematoxylin and eosin stain and immunostaining for CD42b as a marker for platelet aggregates and fibrin.

Results

Fibrin-like fibrinoid is associated with platelet aggregates characterized by the positive immunostaining for CD42b and coagulatory cascade activation with blood flow changes in the circulation and intervillous spaces. Matrix-type fibrinoid is not associated with platelet aggregates and coagulation and its pathogenesis is unknown.

Conclusion

Fibrinoid deposits within the intervillous spaces are mostly from maternal circulation and these fibrinoids are likely the result of the laminar blood flow change at specific anatomic locations, leading to activation of coagulatory cascade. The pathogenesis of matrix-like fibrinoid is unclear. CD42b immunostaining is helpful in difficult cases.
Interrogating mechanisms of ssDNA binding to a viral HUH-endonuclease by alanine scanning of an electrostatic patch
Authors: Nelson Andrew , Tompkins Kassidy , Ramirez Maria Paz , Gordon Wendy R.
Published: December 2019

HUH endonucleases (dubbed “HUH-tags”) are small protein domains capable of forming covalent adducts with ssDNA in a sequence-specific manner. Because viral HUH-tags are relatively small, react quickly, and require no chemical modifications to their ssDNA substrate, they have great value as protein fusion tags in biotechnologies ranging from genetic engineering to single-molecule studies. One of the greatest assets of these tags is sequence-specificity to their unique, native Ori sequence in vivo, introducing the possibility of using multiple HUH-tags in multiplexed “one-pot” reactions. However, their mechanism of ssDNA sequence binding and specificity is poorly understood, and there is noted cross-reactivity between tags of closely related species. In order to understand the mechanism of ssDNA binding, we performed an alanine scan along a positively-charged patch of one such HUH-tag, replication-associated protein from Wheat Dwarf Virus (WDV Rep), and characterized the enzymatic activity in both the rate and extent of the reaction. In molecular beacon Stopped-Flow experiments, single point mutants of WDV showed a more than 60% decrease in reaction rate constant, and gel shift assays showed an almost complete lack of activity for some variants for single nucleotide ssDNA substitutions. In all, these findings help allow us to highlight key interactions in WDV-ssDNA binding, and we gain further insight into potential rational engineering of HUH-endonucleases to bind desired sequences of DNA.
Direct therapeutic targeting of SWI/SNF induces epigenetic reprogramming and durable tumor regression in rhabdoid tumor
Authors: Chasse Maggie H. , Johnson Benjamin K. , Boguslawski Elissa A. , Sorensen Katie M. , Heo Lyong , Madaj Zachary B. , Beddows Ian , Foxa Gabrielle E. , Kitchen-Goosen Susan M. , Williams Bart O. , Triche Timothy J. , Grohar Patrick J.
Published: December 2019

Purpose

Rhabdoid tumor is a pediatric cancer characterized by the biallelic inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. SMARCB1 inactivation leads to SWI/SNF redistribution to favor a proliferative dedifferentiated cellular state. Although this deletion is the known oncogenic driver, SWI/SNF therapeutic targeting remains a challenge.

Experimental Design

We define a novel epigenetic mechanism for mithramycin using biochemical fractionation, chromatin immunoprecipitation sequencing (ChIP-seq), and a dual spike-in assay for transposase accessible chromatin sequencing (ATAC-seq). We correlate epigenetic reprogramming with changes with chromatin A/B compartments and promoter accessibility with chromHMM models and RNA-seq. Finally, we demonstrate durable, marked tumor response in an intramuscular rhabdoid tumor xenograft model.

Results

Here we show mithramycin and a second-generation analogue EC8042 evict mutated SWI/SNF from chromatin and are effective in rhabdoid tumor. SWI/SNF blockade triggers chromatin compartment remodeling and promoter reprogramming leading to differentiation and amplification of H3K27me3, the catalytic mark of PRC2. Treatment of rhabdoid rumor xenografts with EC8042 leads to marked, durable tumor regression and differentiation of the tumor tissue into benign mesenchymal tissue, including de novo bone formation.

Conclusion

Overall, this study identifies a novel therapeutic candidate for rhabdoid tumor and an approach that may be applicable to the 20% of cancers characterized by mutated SWI/SNF.

STATEMENT OF TRANSLATIONAL RELEVANCE

There is a tremendous need for novel therapeutic approaches for rhabdoid tumor and the more than 20% of human cancers characterized by dysregulation of the SWI/SNF chromatin remodeling complex. While approaches to target associated complexes, such as PRC2, known to be influenced by dysregulated SWI/SNF are currently being evaluated in the clinic, the direct therapeutic targeting of SWI/SNF has not been explored. Here we identify an inhibitor of SWI/SNF and thoroughly explore the therapeutic development of this compound from a mechanistic and translational perspective thus providing insight into the targeting of this complex as well as a dose, schedule, and biomarker of target inhibition that is immediately clinically translatable.
Transient disruption of the inferior parietal lobule impairs action mindreading
Authors: Patri Jean-François , Koul Atesh , Soriano Marco , Valente Martina , Avenanti Alessio , Cavallo Andrea , Panzeri Stefano , Becchio Cristina
Published: December 2019

Although it is well established that fronto-parietal regions are active during action observation, whether they play a causal role in the ability to “mindread” others’ actions remains controversial. In experiments reported here, we combined offline continuous theta-burst stimulation (cTBS) with computational modeling to reveal single-trial computations in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Participants received cTBS over the left IPL and IFG, in separate sessions, before completing an intention discrimination task or a kinematic discrimination task unrelated to intention. We found that transient disruption of activity of the IPL, but not the IFG, specifically impaired the observer’s ability to judge intention from movement kinematics. Kinematic discrimination unrelated to intention, in contrast, was largely unaffected. Computational analyses revealed that IPL cTBS did not impair the ability to ‘see’ changes in movement kinematics, nor did it alter the weight given to informative versus non-informative kinematic features. Rather, it selectively impaired the ability to link variations in informative features to the correct intention. These results provide the first causal evidence that IPL maps kinematics to intentions.
Beta 1 Integrin Signaling Mediates Pancreatic Ductal Adenocarcinoma Resistance to MEK Inhibition
Authors: Brannon Arthur , Drouillard Donovan , Steele Nina , Sutherland Shadae , Crawford Howard C. , di Magliano Marina Pasca
Published: December 2019

Pancreatic cancer, one of the deadliest human malignancies, has a dismal 5-year survival rate of 9%. The high mortality rate can be attributed to multiple factors, including late diagnosis and lack of effective therapies.KRASis the most commonly mutated gene in pancreatic cancer, but clinical agents that directly target mutant KRAS are not available. Several effector pathways are activated downstream of oncogenic Kras, including MAPK signaling. MAPK signaling can be inhibited by targeting MEK1/2; unfortunately, this approach has been largely ineffective in pancreatic cancer. Here, we set out to identify mechanisms of MEK inhibitor resistance in pancreatic cancer using primary mouse and human 3D organoid cultures. We optimized the culture of pancreatic tumor organoids that utilized Matrigel as a basement membrane mimetic, facilitating polarized growth. Pancreatic tumor organoids recapitulated mutant KRAS dependency and recalcitrance to MEK inhibition. Treatment of the organoids with trametinib, a MEK inhibitor, had only a modest effect on these cultures. We observed that cells adjacent to the basement membrane mimetic Matrigel survived MEK inhibition, while the cells in the interior layers underwent apoptosis. Our findings suggested that basement membrane attachment provided survival signals. We thus targeted integrin β1, a mediator of extracellular matrix contact, and found that combined MEK and integrin β1 inhibition bypassed trametinib resistance. Our data support exploring integrin signaling inhibition as a component of combination therapy in pancreatic cancer.