bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraductal Papillary Mucinous Neoplasms: Have IAP Consensus Guidelines Changed our Approach?
Authors: Pulvirenti Alessandra , Margonis Georgios A. , Morales-Oyarvide Vicente , McIntyre Caitlin A. , Lawrence Sharon A. , Goldman Debra A. , Gonen Mithat , Weiss Matthew J. , Ferrone Cristina R. , He Jin , Brennan Murray F. , Cameron John L. , Lillemoe Keith D. , Kingham T. Peter , Balachandran Vinod , Qadan Motaz , D’Angelica Michael I. , Jarnagin William R. , Wolfgang Christopher L. , Castillo Carlos Fernández-del , Allen Peter J.
Published: December 2019

Objective:

To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes.

Background:

Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease.

Methods:

Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000–2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006–2012), Fukuoka (FCG, after 2012)].

Results:

The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63).

Conclusion:

Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed.
Not ready for prime time: Intermittent versus partial resuscitative endovascular balloon occlusion of the aorta for prolonged hemorrhage control in a highly lethal porcine injury model
Authors: Johnson Michael Austin , Hoareau Guillaume L. , Beyer Carl A. , Caples Connor A. , Spruce Marguerite , Grayson J. Kevin , Neff Lucas P. , Williams Timothy K.
Published: December 2019

BACKGROUND

Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) and intermittent REBOA (iREBOA) are techniques to extend the therapeutic duration of REBOA by balloon titration for distal flow or cyclical balloon inflation/deflation to allow transient distal flow, respectively. We hypothesized that manually titrated pREBOA would reduce blood losses and ischemic burden when compared with iREBOA.

METHODS

Following 20% blood volume controlled hemorrhage, 10 anesthetized pigs underwent uncontrolled hemorrhage from the right iliac artery and vein. Once in hemorrhagic shock, animals underwent 15 minutes of complete zone 1 REBOA followed by 75 minutes of either pREBOA or iREBOA (n = 5/group). After 90 minutes, definitive hemorrhage control was obtained, animals were resuscitated with the remaining collected blood, and then received 2 hours of critical care.

RESULTS

There were no differences in mortality. Animals randomized to iREBOA spent a larger portion of the time at full occlusion when compared with pREBOA (median, 70 minutes; interquartile range [IQR], 70–80 vs. median, 20 minutes; IQR, 20–40, respectively; p = 0.008). While the average blood pressure during the intervention period was equivalent between groups, this was offset by large fluctuations in blood pressure and significantly more rescue occlusions for hypotension with iREBOA. Despite lower maximum aortic flow rates, the pREBOA group tolerated a greater total amount of distal aortic flow during the intervention period (median, 20.9 L; IQR, 20.1–23.0 vs. median, 9.8 L; IQR, 6.8–10.3; p = 0.03) with equivalent abdominal blood losses. Final plasma lactate and creatinine concentrations were equivalent, although iREBOA animals had increased duodenal edema on histology.

CONCLUSION

Compared with iREBOA, pREBOA reduced the time spent at full occlusion and the number of precipitous drops in proximal mean arterial pressure while delivering more distal aortic flow but not increasing total blood loss in this highly lethal injury model. Neither technique demonstrated a survival benefit. Further refinement of these techniques is necessary before clinical guidelines are issued.
Does simulation work? Monthly trauma simulation and procedural training are associated with decreased time to intervention
Authors: Park Caroline , Grant Jennifer , Dumas Ryan P. , Dultz Linda , Shoultz Thomas H. , Scott Daniel J. , Luk Stephen , Abdelfattah Kareem R. , Cripps Michael W.
Published: December 2019

BACKGROUND

Establishing proficiency in specific trauma procedures during surgical residency has been limited to annual courses with limited data on its effect on the delivery of health care and patient outcomes. There is a wide variety of training on content and complexity with recent studies looking at time to imaging or secondary survey. In this study, we implement monthly case-based simulation after initial training on a variety of bedside trauma procedures. The overall goal is to evaluate the effect of simulation on time to specific interventions.

METHODS

This is a prospective, observational study between July 2018 and February 2019 at a single-institution, Level I trauma center with a large surgical residency program. A trauma simulation program was implemented in November 2018 to train and evaluate surgical residents from post-graduate year 1 through 5. All rotating residents participated in an initial course on basic trauma procedures, such as percutaneous sheath placement, tube thoracostomy, and resuscitative thoracotomy followed by an end-of-month simulation. All Level I activations from preintervention starting in July to October 2018 (preintervention) and October 2018 through February 2019 (postintervention) were reviewed; monitored variables included age, sex, mechanism of injury, blunt or penetrating, and time to intervention in the trauma bay. Median times to intervention were recorded with interquartile ranges (IQR). Pearson's coefficient was used to measure the strength of the relationship between simulation and time to patient intervention.

RESULTS

Median time to most interventions improved over time but with more consistent improvement after the implementation of formal simulation and procedural training in November 2018. Median pretraining time for resuscitative thoracotomy was 14 minutes (IQR, 8–32 minutes); posttraining median time was 3 minutes (IQR, 2.7–8 minutes, p = 0.02). Median pretraining time to tube thoracostomy was 13 minutes (IQR, 5.5–19 minutes); posttraining time was 6 minutes (IQR, 4–31 minutes, p = 0.04). Pearson's coefficient (r
2) measured strength of correlation and was highest for tube thoracostomy followed by resuscitative thoracotomy and percutaneous sheath access with r
2 values of 0.46, 0.35, and 0.24, respectively.

CONCLUSION

High-complexity, routine procedural training, and trauma simulation are associated with decreased time to interventions within a short period of time. Routine implementation of a training program emphasizing efficient, effective approaches to bedside procedures is necessary to train our residents in these high-acuity, low-frequency situations. Future investigations are warranted in the effect of simulation on short-term and long-term patient outcomes.

LEVEL OF EVIDENCE

Therapeutic, level III.
Early single-dose treatment with exosomes provides neuroprotection and improves blood-brain barrier integrity in swine model of traumatic brain injury and hemorrhagic shock
Authors: Williams Aaron M. , Bhatti Umar F. , Brown Jordana F. , Biesterveld Ben E. , Kathawate Ranganath G. , Graham Nathan J. , Chtraklin Kiril , Siddiqui Ali Z. , Dekker Simone E. , Andjelkovic Anuska , Higgins Gerald A. , Buller Benjamin , Alam Hasan B.
Published: December 2019

BACKGROUND

Administration of human mesenchymal stem cell (MSC)–derived exosomes can enhance neurorestoration in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). The impact of early treatment with MSC-derived exosomes on brain injury in a large animal model remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on brain swelling and lesion size, blood-based cerebral biomarkers, and blood-brain barrier (BBB) integrity.

METHODS

Female Yorkshire swine were subjected to a severe TBI (12-mm cortical impact) and HS (40% estimated total blood volume). One hour into shock, animals were randomized (n = 5/cohort) to receive either lactated Ringer's (LR; 5 mL) or LR + exosomes (1 × 1012 exosome particles in 5 mL LR). Animals then underwent additional shock (1 hour) followed by normal saline resuscitation. After 6 hours of observation, brain swelling (% increase compared with the uninjured side) and lesion size (mm3) were assessed. Cerebral hemodynamics and blood-based biomarkers of brain injury were compared. Immunofluorescence and RNA sequencing with differential gene expression and pathway analysis were used to assess the integrity of the perilesion BBB.

RESULTS

Exosome-treated animals had significantly less (p < 0.05) brain swelling and smaller lesion size. They also had significantly decreased (p < 0.05) intracranial pressures and increased cerebral perfusion pressures. Exosome-treated animals had significantly decreased (p < 0.05) albumin extravasation and significantly higher (p < 0.05) laminin, claudin-5, and zonula occludens 1 levels. Differential gene expression and pathway analysis confirmed these findings. Serum glial fibrillary acidic protein levels were also significantly lower (p < 0.05) in the exosome-treated cohort at the end of the experiment.

CONCLUSION

In a large animal model of TBI and HS, early treatment with a single dose of MSC-derived exosomes significantly attenuates brain swelling and lesion size, decreases levels of blood-based cerebral biomarkers, and improves BBB integrity.
Anaerohalosphaera lusitana gen. nov., sp. nov., and Limihaloglobus sulfuriphilus gen. nov., sp. nov., isolated from solar saltern sediments, and proposal of Anaerohalosphaeraceae fam. nov. within the order Sedimentisphaerales
Authors: Pradel Nathalie , Fardeau Marie-Laure , Tindall Brian J. , Spring Stefan
Published: December 2019

Two strains of anaerobic, coccoid, saccharolytic, Gram-stain-negative bacteria were isolated from samples of anoxic hypersaline sediments of evaporation ponds in Tavira (Portugal) and Mallorca (Spain). Both isolates were moderately halophilic, neutrophilic and had a temperature optimum at 37 °C. The highest 16S rRNA gene sequence identity values were found with members of the genus

Sedimentisphaera

(84.9–88.2 %) within the order Sedimentisphaerales, class

Phycisphaerae

. The strain SM-Chi-D1T could be assigned to the family

Sedimentisphaeraceae

, while phylogenetic analyses based on 16S rRNA gene sequences and genomic data indicate that strain ST-NAGAB-D1T is both a member of a novel genus and a novel family. SM-Chi-D1T could be distinguished from other cultured members of the

Sedimentisphaeraceae

mainly by the stimulatory effect of sulfur on growth, lack of ethanol production during fermentation and several differences in the cellular fatty acids and polar lipids patterns. Main differential characteristics of ST-NAGAB-D1T were a polytrichous flagellation, the absence of branched chain fatty acids and presence of large proportions of the unsaturated cellular fatty acids C16 : 1
 c9 and C18 : 1
 c11. On the basis of genomic, chemotaxonomic, biochemical and physiological data, we propose the novel species and genera Anaerohalosphaera lusitana gen. nov., sp. nov., and Limihaloglobus sulfuriphilus gen. nov., sp. nov., represented by the type strains ST-NAGAB-D1T (=DSM 103484T=JCM 31926T=KCTC 15600T) and SM-Chi-D1T (=DSM 100118T=JCM 31927T=KCTC 15601T), respectively. In addition, we propose the novel family Anaerohalosphaeraceae fam. nov. to accommodate the genus Anaerohalosphaera.
HIV-1 founder variant multiplicity is determined by the infection stage of the source partner
Authors: Villabona-Arenas Ch. Julián , Hall Matthew , Lythgoe Katrina A. , Gaffney Stephen G. , Regoes Roland R. , Hué Stéphane , Atkins Katherine E.
Published: December 2019

During sexual transmission, the large genetic diversity of HIV-1 within an individual is frequently reduced to one founder variant that initiates infection1. Understanding the drivers of this bottleneck is crucial to develop effective infection control strategies2. Genetic characteristics of the potential founder viruses and events in the recipient partner are both known to contribute to this bottleneck, but little is understood about the importance of the source partner3. To test the hypothesis that the source partner affects the multiplicity of HIV founder variants, we developed a phylodynamic model calibrated using genetic and epidemiological data on all existing transmission pairs for whom the direction of transmission and the infection stage of the source partner are known. Our results demonstrate the importance of infection stage of the source partner, and not exposure route, in determining founder variant multiplicity. Specifically, acquiring infection from someone in the acute (early) stage of infection increases the risk of multiple variant transmission when compared with someone in the chronic (later) stage of infection. This study provides the first direct test of source partner characteristics to explain the low frequency of multiple founder strain infections and can inform clinical intervention study design and interpretation.
Independently Carriage ofIL-1RN*2 AlleleAssociated with Increased Risk of Gastric Cancer in The Sudanese Population
Authors: Idris Abeer Babiker , Ataelmanan Amany Eltayib , Eltaher Sulafa Mohamed , Idris Einas Babiker , Osman Arbab Bashir M. , Idris Ahmed Ibn , Mansour Mohamed , Ibrahim El-Amin Mohamed , Hassan Mohamed A.
Published: December 2019

Background

Helicobacter pyloriis responsible for gastric cancer in approximately tens of millions of patients. Gastric cancer in Sudan represents one of the top causing death among cancers with about 686 cases per year and a 2.7 % mortality rate.IL-1RNVNTR polymorphism has been reported to increase the risk of gastric cancer.

Objective

The purpose of this study was to assess the association of the 86 bp VNTR polymorphism ofIL- 1RNgene and the susceptibility toH. pyloriinfection and gastric cancer in the Sudanese population.

Materials and methods

Genomic DNA was extracted from 114 subjects. Of whom 60 had gastritis and duodenitis, 26 had a peptic ulcer, 16 had gastric cancer and 12 had normal gastroscopy findings.H. pyloriinfection was investigated by specific16S rRNA. AndIL-1RNVNTR polymorphism at intron 2 was genotyped using the PCR method and direct sequencing for random samples.

Results

The positiveH. pyloriinfection rate among participants was 47.37%. There is a lack of a significant difference inIL- 1RNgenotype withH. pyloriinfection (p-value=1.0000). TheIL-1 RN L/Lgenotype was significantly more frequent in a patient with benign disorders (gastritis or duodenitis or peptic ulcer), Odd=6.000 (95% CI =1.750-20.57, P=0.0056). While the heterozygote genotype 2/L was associated with an increased risk of gastric cancer with OR = 12.83 (95% CI = 1.261-130.6, P=0.0302).

Conclusion

Independently carriage ofIL-1RN *2allele was associated with increased risk of gastric cancer in the Sudanese population. Notwithstanding the relatively small sample size of the study population, our findings show that the host genetic can be a useful tool for identifying high-risk individuals among dyspeptic patients; and also underscore the role played by host genetics in gastric carcinogenesis. To the best of our knowledge, this is the first study in Sudan concerning this issue.
Alien limb in the corticobasal syndrome: phenomenological characteristics and relationship to apraxia
Authors: Lewis-Smith David J. , Wolpe Noham , Ghosh Boyd C.P. , Rowe James B.
Published: December 2019

Alien limb refers to movements that seem purposeful but are independent of patients’ reported intentions. Alien limb often co-occurs with apraxia in the corticobasal syndrome, and anatomical and phenomenological comparisons have led to the suggestion that alien limb and apraxia may be causally related as failures of goal-directed movements. Here, we characterised the nature of alien limb symptoms in patients with the corticobasal syndrome (n=30) and their relationship to limb apraxia. Twenty-five patients with progressive supranuclear palsy Richardson syndrome served as a disease-control group. Structured examinations of praxis, motor function, cognition and alien limb were undertaken in patients attending a regional specialist clinic. Twenty-eight patients with corticobasal syndrome (93%) demonstrated significant apraxia and this was often asymmetrical, with the left hand preferentially affected in 77% of patients. Moreover, 83% reported one or more symptoms consistent with alien limb. The range of these phenomena was broad, including changes in the sense of ownership and control as well as unwanted movements. Regression analyses showed no significant association between the severity of limb apraxia and both the occurrence of an alien limb and the number of alien limb phenomena reported. Bayesian estimation showed a low probability for a positive association between alien limb and apraxia, suggesting that alien limb phenomena are not likely to be related to severe apraxia. Our results shed light on the phenomenology of these disabling and as yet untreatable clinical features, with relevance to theoretical models of voluntary action.
Making densenet interpretable a case study in clinical radiology
Authors: Ngan Kwun Ho , Garcez Artur d’Avila , Knapp Karen M. , Appelboam Andy , Reyes-Aldasoro Constantino Carlos
Published: December 2019

The monotonous routine of medical image analysis under tight time constraints has always led to work fatigue for many medical practitioners. Medical image interpretation can be error-prone and this can increase the risk of an incorrect procedure being recommended. While the advancement of complex deep learning models has achieved performance beyond human capability in some computer vision tasks, widespread adoption in the medical field has been held back, among other factors, by poor model interpretability and a lack of high-quality labelled data. This paper introduces a model interpretation and visualisation framework for the analysis of the feature extraction process of a deep convolutional neural network and applies it to abnormality detection using the musculoskeletal radiograph dataset (MURA, Stanford). The proposed framework provides a mechanism for interpreting DenseNet deep learning architectures. It aims to provide a deeper insight about the paths of feature generation and reasoning within a DenseNet architecture. When evaluated on MURA at abnormality detection tasks, the model interpretation framework has been shown capable of identifying limitations in the reasoning of a DenseNet architecture applied to radiography, which can in turn be ameliorated through model interpretation and visualization.
Measurement of Prostate Volume with MRI (A Guide for the Perplexed): Biproximate Method with Analysis of Precision and Accuracy
Authors: Wasserman Neil F. , Niendorf Eric , Spilseth Benjamin
Published: December 2019

Purpose

To review the anatomic basis of prostate boundary selection on T2-weighted magnetic resonance imaging (MRI). To introduce an alternative 3D ellipsoid measuring technique that maximizes precision, report the intra- and inter-observer reliability, and to advocate it’s use for research involving multiple observers.

Methods

A demonstration of prostate boundary anatomy using gross pathology and MRI examples provides background for selection of key boundary marks when measuring prostate volume. An alternative ellipsoid volume method is illustrated. An IRB approved retrospective study of 140 patients with elevated serum prostate specific antigen levels and/or abnormal digital rectal examinations was done with T2-weighted MRI applying the new (Biproximate) technique. Measurements were made by 2 examiners, correlated with each other for interobserver precision and with an expert observer for accuracy. Correlation statistics, linear regression analysis, and tests of means were applied using p≤0.05 as the threshold for significance.

Results

Inter-observer correlation (precision) was 0.95 between observers. Correlation between these observers and the expert (accuracy) was 0.94 and 0.97 respectively. Intra-observer correlation for the expert was 0.98. Means for inter-rater reliability and accuracy were all the same (p=0.001).

Conclusions

Anatomic foundations for the boundaries of the prostate are reviewed. Precision and accuracy of total prostate volume using an alternative method is reported and found to be reproducible.
The smfBox: an open-source platform for single-molecule FRET
Authors: Ambrose Benjamin , Baxter James , Cully John , Willmott Matthew , Steele Elliot , Bateman Benji C. , Martin-Fernandez Marisa L. , Cadby Ashley , Shewring Jonathan , Aaldering Marleen , Craggs Timothy D.
Published: December 2019

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful technique capable of resolving both relative and absolute distances within and between structurally dynamic biomolecules. High instrument costs, and a lack of open-source hardware and acquisition software have limited smFRET’s broad application by non-specialists. Here, we present the smfBox, a cost-effective confocal smFRET platform, providing detailed build instructions, open-source acquisition software, and full validation, thereby democratising smFRET for the wider scientific community.
Single-cell RNA-seq reveals CD16-monocytes as key regulators of human monocyte transcriptional response toToxoplasma
Authors: Patir Anirudh , Gossner Anton , Ramachandran Prakash , Alves Joana , Freeman Tom C. , Henderson Neil C. , Watson Michael , Hassan Musa A.
Published: December 2019

Monocytes are among the major myeloid cells that respond toToxoplasma, a ubiquitous foodborne that infects ≥1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasmainteractions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasmainteractions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses toToxoplasmahave sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte response to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasmaencounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report thatToxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14++CD16-monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover theToxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed toToxoplasma.
Osteoblast-osteoclast co-culture amplifies inhibitory effects of FG-4592 on osteoclast formation and reduces bone resorption activity
Authors: Hulley Philippa A , Papadimitriou-Olivgeri Ioanna , Knowles Helen J
Published: December 2019

The link between bone and blood vessels is regulated by hypoxia and the hypoxia-inducible transcription factor, HIF, which drives both osteogenesis and angiogenesis. The recent clinical approval of PHD enzyme inhibitors, which stabilise HIF protein, introduces the potential for a new clinical strategy to treat osteolytic conditions such as osteoporosis, osteonecrosis and skeletal fracture and non-union. However, bone-resorbing osteoclasts also play a central role in bone remodelling and pathological osteolysis and HIF promotes osteoclast activation and bone loss in vitro. It is therefore likely that the final outcome of PHD enzyme inhibition in vivo would be mediated by a balance between increased bone formation and increased bone resorption. It is essential that we improve our understanding of the effects of HIF on osteoclast formation and function, and consider the potential contribution of inhibitory interactions with other musculoskeletal cells.

The PHD enzyme inhibitor FG-4592 stabilised HIF protein and stimulated osteoclast-mediated bone resorption, but inhibited differentiation of human CD14+ monocytes into osteoclasts. Formation of osteoclasts in a more physiologically relevant 3D collagen gel did not affect the sensitivity of osteoclastogenesis to FG-4592, but increased sensitivity to reduced concentrations of RANKL. Co-culture with osteoblasts amplified inhibition of osteoclastogenesis by FG-4592, whether the osteoblasts were proliferating, differentiating or in the presence of exogenous M-CSF and RANKL. Osteoblast co-culture dampened the ability of high concentrations of FG-4592 to increase bone resorption.

This data provides support for the therapeutic use of PHD enzyme inhibitors to improve bone formation and/or reduce bone loss for treatment of osteolytic pathologies, and indicates that FG-4592 might also act to inhibit the formation and activity of the osteoclasts that drive osteolysis.
Color tuning of neurons in face patches of macaque inferior temporal cortex
Authors: Duyck Marianne , Gruen Tessa J. , Tello Lawrence Y. , Eastman Serena , Fuller-Deets Joshua , Conway Bevil R.
Published: December 2019

Previous work has shown that under viewing conditions that break retinal mechanisms for color, one class of objects appears paradoxically colored: faces, and they look green. Interpreted within a Bayesian-observer framework, this observation makes the surprising prediction that face-selective neurons are sensitive to color and weakly biased for colors that elicit L>M cone activity (warm colors). We tested this hypothesis by measuring color-tuning responses of face-selective cells in alert macaque monkey, using fMRI-guided microelectrode recording of the middle and anterior face patches and carefully color-calibrated stimuli. The population of face-selective neurons showed significant color tuning when assessed using images that preserved the luminance contrast relationships of the original face photographs. A Fourier analysis of the color-tuning responses uncovered two components. The first harmonic was biased towards the L>M colors, consistent with the prediction. Interestingly, the second harmonic aligned with the S-cone cardinal axis, which may relate to the computation of animacy by IT cells.

Significance

The results provide the first quantitative measurements of the color tuning properties of face-selective neurons. The results provide insight into the neural mechanisms that could support the role of color in face perception.
Spatial, climate, and ploidy factors drive genomic diversity and resilience in the widespread grassThemeda triandra
Authors: Ahrens CW , James EA , Miller AD , Aitken NC , Borevitz JO , Cantrill DJ , Rymer PD
Published: December 2019

Fragmented grassland ecosystems, and the species that shape them, are under immense pressure. Restoration and management strategies should include genetic diversity and adaptive capacity to improve success but these data are generally unavailable. Therefore, we use the foundational grass,Themeda triandra, to test how spatial, environmental, and ploidy factors shape patterns of genetic variation.

We used reduced-representation genome sequencing on 487 samples from 52 locations to answer fundamental questions about how the distribution of genomic diversity and ploidy polymorphism supports adaptation to harsher climates. We explicitly quantified isolation-by-distance (IBD), isolation-by-environment (IBE), and predicted population genomic vulnerability in 2070.

We found that a majority (54%) of the genomic variation could be attributed to IBD, while 22% of the genomic variation could be explained by four climate variables showing IBE. Results indicate that heterogeneous patterns of vulnerability across populations are due to genetic variation, multiple climate factors, and ploidy polymorphism, which lessened genomic vulnerability in the most susceptible populations.

These results indicate that restoration and management ofT. triandrashould incorporate knowledge of genomic diversity and ploidy polymorphisms to increase the likelihood of population persistence and restoration success in areas that will become hotter and more arid.
Attraction, Dynamics, and Phase Transitions in Fire Ant Tower-Building
Authors: Nave Gary K. , Mitchell Nelson T. , Dick Jordan A. Chan , Schuessler Tyler , Lagarrigue Joaquin A. , Peleg Orit
Published: December 2019

Many insect species, and even some vertebrates, assemble their bodies to form multi-functional materials that combine sensing, computation, and actuation. The tower-building behavior of red imported fire ants, Solenopsis invicta, presents a key example of this phenomenon of collective construction. While biological studies of collective construction focus on behavioral assays to measure the dynamics of formation and studies of swarm robotics focus on developing hardware that can assemble and interact, algorithms for designing such collective aggregations have been mostly overlooked. We address this gap by formulating an agent-based model for collective tower-building with a set of behavioral rules that incorporate local sensing of neighboring agents. We find that an attractive force makes tower building possible. Next, we explore the trade-offs between attraction and random motion to characterize the dynamics and phase transition of the tower building process. Lastly, we provide an optimization tool that may be used to design towers of specific shapes, mechanical loads, and dynamical properties such as mechanical stability and mobility of the center of mass.
Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning
Authors: Smith Martin A. , Ersavas Tansel , Ferguson James M. , Liu Huanle , Lucas Morghan C , Begik Oguzhan , Bojarski Lilly , Barton Kirston , Novoa Eva Maria
Published: December 2019

Nanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5’ and 3’ ends of reads, which complicates sequence-based barcode demultiplexing. Here, we propose a novel strategy to barcode and demultiplex direct RNA sequencing nanopore data, which does not rely on base-calling or additional library preparation steps. Specifically, custom DNA oligonucleotides are ligated to RNA transcripts during library preparation. Then, raw current signal corresponding to the DNA barcode is extracted and transformed into an array of pixels, which is used to determine the underlying barcode using a deep convolutional neural network classifier. Our method,DeePlexiCon, implements a 20-layer residual neural network model that can demultiplex 93% of the reads with 95.1% specificity, or 60% of reads with 99.9% specificity. The availability of an efficient and simple barcoding strategy for native RNA sequencing will enhance the use of direct RNA sequencing by making it more cost-effective to the entire community. Moreover, it will facilitate the applicability of direct RNA sequencing to samples where the RNA amounts are limited, such as patient-derived samples.
Variation of bacterial communities along the vertical gradient in Lake Issyk Kul, Kyrgyzstan
Authors: Rojas-Jimenez Keilor , Araya-Lobo Alex , Quesada-Perez Fabio , Akerman-Sanchez Johana , Delgado-Duran Brayan , Ganzert Lars , Zavialov Peter O. , Alymkulov Salmor , Kirillin Georgiy , Grossart Hans Peter
Published: December 2019

In this study, we explored the diversity and community composition of bacteria along a vertical gradient in Lake Issyk Kul, Kyrgyzstan, one of the largest and deepest brackish lakes in in the world. We identified 4904 bacterial ASVs based on analysis of 16S rRNA gene sequences and determined significant changes in the composition responding mainly to the variables depth and salinity. A higher abundance of Proteobacteria and Bacteroidetes was observed in the surface waters and the lake tributaries. Cyanobacteria were more abundant in the deep chlorophyll maximum (28.5 to 128 m), while Planctomycetes and Chloroflexi were dominant at depths between 128 to 600 m. According to our machine learning analysis used for identifying the most critical environmental factors, depth and temperature revealed the strongest effect on members of Proteobacteria, Planctomycetes, and Chloroflexi, while oxygen is associated with the variations in Cyanobacteria. Also, a notable increase in alpha diversity estimations was observed with increasing water depth. This work evidences significant differences in the structure of bacterial communities along the depth gradient in deep, transparent lake ecosystems. Notably, there is a dominance of Planctomycetes and Chloroflexi in the deepest layers, which can only be seen in a few other lakes with similar characteristics as Lake Issyk Kul and raises questions about their ecological role.
Antibiograms and Molecular Characterization of Drug Resistance ofMycobacterium abscessuscomplex from Patients with Multidrug-Resistant Pulmonary Tuberculosis (MDR TB) Infection
Authors: Bongulto Kenneth A. , Ang Concepcion F. , Cabrera Esperanza C.
Published: December 2019

In the Philippines, acid fast bacilli positive sputum samples commonly treated as TB due toMycobacterium tuberculosis(MTB) complex. However,Mycobacterium abscessus(MAB) complex is often found in MTB cultures, or in patients confirmed negative for TB through sputum microscopy and culture. Hence, patients with MAB infections are mistakenly prescribed six-month anti-TB treatments. In this study, MAB complex isolates from MDRTB patients were identified and further sub-speciated using themass3210 gene. Antimicrobial susceptibility was tested using broth microdilution and resistance geneserm(41),rrs, rrl, gyrA, andgyrB were studied for mutations. Majority were susceptible to amikacin, azithromycin, clarithromycin, and moxifloxacin [MAB: 100%, 100%, 100%, 81.8%, respectively;M. massiliense(MAM): 100%, 100%, 100%, 60%, respectively]. 50% MAM and 63.6% MAB were susceptible to cefoxitin; 60% MAM and 45.5% MAB were susceptible to ciprofloxacin; 72.7% MAB, and 10%MAM were susceptible to doxycycline. Inducible resistance to azithromycin and clarithromycin was found in 27.3%MAB and 30% MAM. 42.9% MAB complex isolates were MDR. Macrolide resistant MAB and MAM had T28 sequevar, showing functionalerm(41) responsible for inducible resistance. Unexpectedly, full lengtherm(41) was found in MAM. Therrlgene in these isolates showed no point mutations, indicating T28 sequevar as cause of inducible resistance. All fluoroquinolone resistant isolates showed Ala-83 ingyrA fluoroquinolone resistant-dependent region (QRDR) and Arg-447 and Asn-464 ingyrB QRDR. These are associated with resistance to the drug.
Twinfilin uncaps filament barbed ends to promote turnover of lamellipodial actin networks
Authors: Hakala Markku , Wioland Hugo , Tolonen Mari , Jegou Antoine , Romet-Lemonne Guillaume , Lappalainen Pekka
Published: December 2019

Coordinated polymerization of actin filaments provides force for cell migration, morphogenesis, and endocytosis. Capping Protein (CP) is central regulator of actin dynamics in all eukaryotes. It binds actin filament (F-actin) barbed ends with high affinity and slow dissociation kinetics to prevent filament polymerization and depolymerization. In cells, however, CP displays remarkably rapid dynamics within F-actin networks, but the underlying mechanism has remained enigmatic. We report that a conserved cytoskeletal regulator, twinfilin, is responsible for CP’s rapid dynamics and specific localization in cells. Depletion of twinfilin led to stable association of CP with cellular F-actin arrays and its treadmilling throughout leading-edge lamellipodium. These were accompanied by diminished F-actin disassembly rates. In vitro single filament imaging approaches revealed that twinfilin directly promotes dissociation of CP from filament barbed ends, while allowing subsequent filament depolymerization. These results uncover an evolutionary conserved bipartite mechanism that controls how actin cytoskeleton-mediated forces are generated in cells.
Correlated evolution between heat tolerance and thermal performance curves in Drosophila subobscura
Authors: Mesas Andrés , Jaramillo Angélica , Castañeda Luis E.
Published: December 2019

Global warming imposes important challenges for ectotherm organisms, which can avoid the negative effects of thermal stress via evolutionary adaptation of their upper thermal limits (CTmax). In this sense, the estimation of CTmax and its evolutionary capacity is crucial to determine the vulnerability of natural populations to climate change. However, these estimates depend on the thermal stress intensity and it is not completely clear whether this thermal stress intensity can impact the evolutionary response of CTmax and thermal reaction norms (i.e. thermal performance curve, TPC). Here we performed an evolutionary experiment by selecting high heat tolerance using acute and chronic thermal stress in Drosophila subobscura. After artificial selection, we found that knockdown temperatures (a CTmax proxy) evolved in selected lines compared to control lines, whereas the realized heritability and evolutionary rate change of heat tolerance did not differ between acute-selected and chronic-selected lines. From TPC analysis, we found acute-selected lines evolved a higher optimal performance temperature (Topt) compared to acute-control lines, whereas this TPC parameter was not different between chronic-selected and chronic-control lines. The evolutionary response of Topt caused a displacement of entire TPC to high temperatures suggesting a shared genetic architecture between heat tolerance and high-temperature performance, which only arose in the acute-selected lines. In conclusion, thermal stress intensity has important effects on the evolution of thermal physiology in ectotherms, indicating that different thermal scenarios conduce to similar evolutionary responses of heat tolerance but do not for thermal performance. Therefore, thermal stress intensity could have important consequences on the estimations of the vulnerability of ectotherms to global warming.
Model for disordered proteins with strongly sequence-dependent liquid phase behavior
Authors: Statt Antonia , Casademunt Helena , Brangwynne Clifford P. , Panagiotopoulos Athanassios Z.
Published: December 2019

Phase separation of intrinsically disordered proteins is important for the formation of membraneless organelles, or biomolecular condensates, which play key roles in the regulation of biochemical processes within cells. In this work, we investigated the phase separation of different sequences of a coarse-grained model for intrinsically disordered proteins and discovered a surprisingly rich phase behavior. We studied both the fraction of total hydrophobic parts and the distribution of hydrophobic parts. Not surprisingly, sequences with larger hydrophobic fractions showed conventional liquid-liquid phase separation. The location of the critical point was systematically influenced by the terminal beads of the sequence, due to changes in interfacial composition and tension. For sequences with lower hydrophobicity, we observed not only conventional liquid-liquid phase separation, but also reentrant phase behavior, in which the liquid phase density decreases at lower temperatures. For some sequences, we observed formation of open phases consisting of aggregates, rather than a normal liquid. These aggregates had overall lower densities than the conventional liquid phases, and exhibited complex geometries with large interconnected string-like or membrane-like clusters. Our findings suggest that minor alterations in the ordering of residues may lead to large changes in the phase behavior of the protein, a fact of significant potential relevance for biology.
Cultivation of Exoelectrogenic Bacteria in Conductive DNA Nanocomposite Hydrogels Yields a Programmable Biohybrid Materials System
Authors: Hu Yong , Rehnlund David , Klein Edina , Gescher Johannes , Niemeyer Christof M.
Published: December 2019

The use of living microorganisms integrated within electrochemical devices is an expanding field of research, with applications in microbial fuel cells, microbial biosensors or bioreactors. We describe the use of porous nanocomposite materials prepared by DNA polymerization of carbon nanotubes (CNT) and silica nanoparticles (SiNP) for the construction of a programmable biohybrid system containing the exoelectrogenic bacterium Shewanella oneidensis. We initially demonstrate the electrical conductivity of the CNT-containing DNA composite by employment of chronopotentiometry, electrochemical impedance spectroscopy, and cyclic voltammetry. Cultivation of Shewanella oneidensis in these materials shows that the exoelectrogenic bacteria populate the matrix of the composite, while non-exoelectrogenic Escherichia coli remain on its surface. Moreover, the ability to use extracellular electron transfer pathways is positively correlated with number of cells within the conductive synthetic biofilm matrix. The Shewanella containing composite remains stable for several days. Programmability of this biohybrid material system is demonstrated by on-demand release and degradation induced by a short-term enzymatic stimulus. The perspectives of this approach for technical applications are being discussed.
An unsupervised feature extraction and selection strategy for identifying epithelial-mesenchymal transition state metrics in breast cancer and melanoma
Authors: Klinke David J. , Torang Arezo
Published: December 2019

Digital cytometry is opening up new avenues to better understand the heterogeneous cell types present within the tumor microenvironment. While the focus is towards elucidating immune and stromal cells as clinical correlates, there is still a need to better understand how a change in tumor cell phenotype, such as the epithelial-mesenchymal transition, influences the immune contexture. To complement existing digital cytometry methods, our objective was to develop an unsupervised gene signature capturing a change in differentiation state that is tailored to the specific cellular context of breast cancer and melanoma, as a illustrative example. Towards this aim, we used principal component analysis coupled with resampling to develop unsupervised gene expression-based state metrics specific for the cellular context that characterize the state of cellular differentiation within an epithelial to mesenchymal-like state space and independently correlate with metastatic potential. First developed using cell line data, the orthogonal state metrics were refined to exclude the contributions of normal fibroblasts and to provide tissue-level state estimates based on bulk tissue RNA-seq measures. The resulting gene expression-based metrics for differentiation state aim to inform a more holistic view of how the malignant cell phenotype influences the immune contexture within the tumor microenvironment.
Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review
Authors: Onwuchekwa Chukwuemeka , Bassey Edem , Williams Victor , Oga Emmanuel
Published: December 2019

Background

The impact of pneumococcal conjugate vaccine introduction in reducing the incidence of childhood pneumonia has not been well documented in sub-Saharan Africa. Many studies evaluating vaccine impact have used invasive pneumococcal disease or pneumococcal pneumonia as an outcome.

Objective

To estimate the impact of routine administration of 10-valent and 13-valent PCV on the incidence of pneumonia in children under five years of age in sub-Saharan Africa.

Data sources

A systematic review was conducted between 16 and 31 July 2019. The review was registered on PROSPERO with registration number CRD42019142369. The literature search was conducted in indexed databases including Medline and Embase, grey literature databases and online libraries of two universities. Manual search of the references of included studies was performed to identify additional relevant studies. The search strategy combined pneumococcal conjugate vaccine, pneumonia and child as search concepts.

Study selection

Studies investigating the impact of 10- or13-valent PCV on childhood pneumonia in a sub-Saharan African country were eligible for inclusion. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Exclusion criteria were use of 7- or 9-valent PCV, systematic review studies, clinical trials and record publication prior to 2009.

Data extraction

Independent data extraction was conducted. Key variables include year study conducted, type of study design, type of PCV used and year of introduction, reported PCV coverage, outcome measure evaluated and the effect measure.

Data synthesis

Eight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact measured as percentage reduction in risk (%RR) of clinical pneumonia was mostly small and non-significant. The risk reduction was more significant and consistent on radiological and pneumococcal pneumonia. Vaccine effectiveness reported in case-control studies was mostly non-significant.

Conclusion

Evidence of the positive impact of routine infant pneumococcal vaccination on pneumonia in sub-Saharan Africa is weak. There is a need for more research in this area to evaluate the influence of pathogen or serotype replacement in pneumonia after PCV introduction. Ongoing surveillance is also required to establish the long term trend in pneumonia epidemiology after PCV introduction.