bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Nonpalliative Medications Following Burdensome Health Care Transitions in Hospice Patients
Authors: Zueger Patrick M. , Holmes Holly M. , Qato Dima M. , Pickard A. Simon , Calip Gregory S. , Lee Todd A.
Published: October 2018

Background:

Limited benefit medications (LBMs), those medications with questionable benefit at the end of life, are often recommended for discontinuation in hospice patients. Transitions in care are associated with inappropriate prescribing in older and terminally ill populations.

Objectives:

To evaluate the association between burdensome health care transitions and subsequent receipt of LBMs in older hospice patients.

Methods:

We conducted a matched cohort analysis of patients admitted to hospice between 2008 and 2013 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The prevalence of post–health care transition LBM use was assessed. Adjusted incidence rate ratios (IRRs) were estimated for the association between transitions and subsequent receipt of LBMs.

Results:

In total, 17.9% of 7064 hospice patients received at least 1 LBM following their first burdensome health care transition. Posttransition continuation of a medication class used before hospice admission was most common for antidementia medications (14.2%) and antihypertensives (11.2%). Transitions were associated with a 33% increase in the risk of receiving at least 1 LBM [IRR, 1.33; 95% confidence interval (CI), 1.25–1.42], increasing to 56% when evaluating only hospitalization transitions (IRR, 1.56; 95% CI, 1.39–1.76). Medication classes more likely to be dispensed after a transition included antihyperlipidemics (IRR, 1.38; 95% CI, 1.13–1.70), antihypertensives (IRR, 1.28; 95% CI, 1.16–1.40), and proton-pump inhibitors (IRR, 1.40; 95% CI, 1.20–1.63).

Conclusions:

Burdensome health care transitions were associated with the receipt of nonpalliative medications in older hospice patients. Interventions aimed at improving provider communication and reducing fragmentation in care may help reduce unnecessary medication use in this vulnerable population.
Nivolumab in the Treatment of Recurrent or Refractory Pediatric Brain Tumors: A Single Institutional Experience
Authors: Gorsi Hamza S. , Malicki Denise M. , Barsan Valentin , Tumblin Mark , Yeh-Nayre Lanipua , Milburn Mehrzad , Elster Jennifer D. , Crawford John R.
Published: October 2018

Successful use of immune checkpoint inhibitors in a variety of cancers has generated interest in using this approach in pediatric brain tumors. We performed a retrospective review of 10 consecutive children (6 boys, 4 girls; ages, 2 to 17 y), with recurrent or refractory pediatric brain tumors (5 high-grade glioma, 1 low-grade glioma, pineoblastoma, medulloblastoma, ependymoma, and CNS embryonal tumor, NOS) treated at Rady Children’s Hospital San Diego from 2015 to 2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 wk). Eight of 10 patients received prior chemotherapy and 9 radiation therapy. Nine patients had radiographic disease progression (median, 2.5 doses). Median time to progression was 5.5 weeks (1.6 to 24 wk). Three patients (2 with high-grade glioma, 1 with CNS embryonal tumor NOS) showed a partial response to treatment at the primary tumor site and 2 of 3 had progression of metastatic disease. Grade 2 toxicities were observed without dose limiting side effects. Tumor mutation burden (TMB) was low to intermediate (median, 1.3; range, 0 to 6.3). Median survival for PD-L1 positive patients was 13.7 weeks versus 4.2 weeks for PD-L1 negative patients (ρ=0.08) nivolumab was well tolerated in our series of pediatric recurrent brain tumors with some transient partial responses in patients with positive PD-L1 expression and higher TMB. Our findings suggest that the use of immune checkpoint inhibitors in pediatric brain tumor patients should be limited to those with elevated PD-L1 expression and TMB.
Tranexamic Acid for Prevention and Treatment of Postpartum Hemorrhage: An Update on Management and Clinical Outcomes
Authors: Ahmadzia Homa K. , Phillips Jaclyn M. , Katler Quinton S. , James Andra H.
Published: October 2018

Importance

Postpartum hemorrhage (PPH) remains a major cause of maternal mortality worldwide, occurring in both vaginal and cesarean deliveries. We have witnessed improvements in both prevention and treatment of PPH. Tranexamic acid (TXA) has been investigated as a potential adjunct therapy to uterotonics within this setting.

Objective

The aim of this article is to summarize existing recommendations on the use of TXA in obstetrics and review current data on clinical outcomes after TXA use.

Evidence Acquisition

We reviewed guidelines from a number of professional societies and performed an extensive literature search reviewing relevant and current data in this area.

Results and Conclusions

In the prevention of PPH, TXA use before both vaginal and cesarean deliveries reduces the amount of postpartum blood loss and should be considered in patients at higher risk for hemorrhage. In the treatment of PPH, TXA should be initiated early for maximal survival benefit from hemorrhage, and it provides no additional benefit if administered more than 3 hours from delivery. Overall, current evidence assessing the risks of TXA use in an obstetric population is reassuring.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to: define the mechanism of action of TXA; evaluate the utility of TXA in prophylaxis and treatment of PPH; define common doses of TXA used in the peripartum period; and assess associated risk and possible adverse outcome when using TXA.
Promoting Risk Identification and Reduction of Cardiovascular Disease in Women Through Collaboration With Obstetricians and Gynecologists: A Presidential Advisory From the American Heart Association and the American College of Obstetricians and Gynecologists
Authors: Brown Haywood L. , Warner John J. , Gianos Eugenia , Gulati Martha , Hill Alexandria J. , Hollier Lisa M. , Rosen Stacey E. , Rosser Mary L. , Wenger Nanette K.
Published: October 2018

(Abstracted from Circulation 2018;137(24):e843–e852)

Many traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, such as hypertension, diabetes mellitus, hypercholesterolemia, and obesity, may affect women more than men and in many cases more severely. Cardiovascular mortality is greater in women than in men.
Analgesic Use and Ovarian Cancer Risk: An Analysis in the Ovarian Cancer Cohort Consortium
Authors: Trabert Britton , Poole Elizabeth M. , White Emily , Visvanathan Kala , Adami Hans-Olov , Anderson Garnet L. , Brasky Theodore M. , Brinton Louise A. , Fortner Renee T. , Gaudet Mia , Hartge Patricia , Hoffman-Bolton Judith , Jones Michael , Lacey James V. , Larsson Susanna C. , Mackenzie Gerardo G. , Schouten Leo J. , Sandler Dale P. , O'Brien Katie , Patel Alpa V. , Peters Ulrike , Prizment Anna , Robien Kim , Setiawan Wendy V. , Swerdlow Anthony , van den Brandt Piet A. , Weiderpass Elisabete , Wilkens Lynne R. , Wolk Alicja , Wentzensen Nicolas , Tworoger Shelley S.
Published: October 2018

(Abstracted from J Natl Cancer Inst 2018; doi: 10.1093/jnci/djy100)

The most fatal gynecologic cancer is ovarian cancer. This is largely due to its delayed symptom presentation and lack of early detection strategies.
Systematic Review of the Clinical Efficacy of Vaginal Progesterone for Luteal Phase Support in Assisted Reproductive Technology Cycles
Authors: Child Tim , Leonard Saoirse A. , Evans Jennifer S. , Lass Amir
Published: October 2018

(Abstracted from Reprod Biomed Online 2018;36:630–645)

Sufficient luteal phase support (LPS) is essential during assisted reproductive technology (ART) cycles to improve implantation and pregnancy rates. The most common route for LPS in Europe is vaginal progesterone via capsule, gel, or tablet.
Rapid Syphilis Testing for Men Who Have Sex With Men in Outreach Settings: Evaluation of Test Performance and Impact on Time to Treatment
Authors: Obafemi Oluyomi A. , Wendel Karen A. , Anderson Teri S. , Scott Tracy E. , Rowan Sarah E. , Travanty Emily A. , Rietmeijer Cornelis A.
Published: October 2018

Background

Rapid syphilis tests (RST) may shorten time to syphilis diagnosis and treatment while enhancing access to testing in outreach settings. There are limited data on the performance of RST in outreach settings in the US.

Methods

We offered RST (Syphilis Health Check) at 6 outreach sites to men who reported having sex with men and no prior history of syphilis. Clients accepting RST were also tested with laboratory-based rapid plasma reagin (RPR) and reflex Treponema pallidum particle agglutination (TPPA) assay when RPR or RST were positive. Clients with positive RST were immediately referred to a sexually transmitted infection clinic. Those declining RST were screened with RPR and reflex TPPA only. The validity of the RST-based algorithm was compared with the RPR-based algorithm among participants receiving both. Time to treatment for those accepting RST was compared with those declining RST and to a historical control group screened in outreach settings with RPR and reflex TPPA before the availability of RST.

Results

Rapid syphilis test was accepted by 690 (64%) of 1081 eligible clients. Compared with RPR-based algorithm, RST sensitivity was 90%; specificity, 98.5%; positive predictive value, 47.4%; and negative predictive value, 98.5. The single false-negative case by RST was determined to be a late latent case by RPR/TPPA. Median time to treatment was 1 day (range, 0–6 days) for 9 of 690 accepting RST, compared to 9 days (range, 7–13 days) for 3 of 391 declining RST, and 9 days (range, 6–21 days) for 25 of 1229 historical controls (P < 0.0001).

Conclusion

Compared with an RPR-based algorithm, RST identified all early syphilis cases. Although RST had high specificity and negative predictive value, the low positive predictive value resulted in additional assessments in a sexually transmitted infection clinic for some patients. However, RST use in outreach settings significantly decreased time to treatment for new syphilis cases.
Sudden, Unexpected Death Due to Pseudo-Meigs Syndrome
Authors: Barranco Rosario , Molinelli Andrea , Gentile Raffaella , Ventura Francesco
Published: October 2018

Meigs syndrome is the triad of ascites, hydrothorax, and benign ovarian tumor (mostly fibroids). It is a diagnosis of exclusion, and the characteristic symptoms disappear after resection of the tumor. Instead, in Pseudo-Meigs syndrome, the triad includes a nonfibroma ovarian tumor. The latter may consist of benign tumors (ie, of fallopian tube or uterus, struma ovarii, and ovarian leiomyomas) but can also comprise ovarian or metastatic gastrointestinal malignancies.

The authors describe a case of sudden death in a 43-year-old woman, with no noteworthy reported history of present illness or medical history and in apparently good health before death.

The autopsy showed a picture of bilateral hydrothorax with lung collapse, ascites, and a large left-sided ovarian mass, approximately 15 cm in diameter. Histopathological examinations revealed an ovarian epithelial malignancy (cystadenocarcinoma). There was also lung atelectasis with accompanying thrombosis of small and medium blood vessels. The combination of autopsy and histological findings allowed us to establish the diagnosis of Pseudo-Meigs syndrome, undiagnosed antemortem, resulting in death due to pulmonary and thrombotic complications. Our subsequent review of the literature found no case reports of undiagnosed Pseudo-Meigs syndrome presenting as sudden death, highlighting the uniqueness of the case presented herein.
Pouch Versus No Pouch Following Total Gastrectomy: Meta-analysis of Randomized and Non-randomized Studies
Authors: Syn Nicholas L. , Wee Ian , Shabbir Asim , Kim Guowei , So Jimmy Bok-Yan
Published: October 2018

Objective:

The aim of the study was to assess the impact of pouch reconstruction on perioperative outcomes, postprandial symptoms, nutritional and anthropometric parameters, and overall quality of life after total gastrectomy for gastric malignancy.

Summary Background Data:

The short-term perioperative risks and longer term functional value of creating a small-bowel reservoir after total gastrectomy are contended.

Methods:

A search for randomized and non-randomized studies comparing reconstruction with or without a pouch was conducted. Treatment effects were computed using pairwise random-effects meta-analysis and meta-regression, and the systematic review was conducted in accordance with PRISMA and MOOSE guidelines.

Results:

A total of 17 randomized trials and 8 observational studies involving 1621 participants were included. Pouch creation is associated with an increased operation time [259.3 vs 235.8 min; weighted mean difference (WMD) 23.5, 95% confidence interval (CI) 9.8–37.2], but not hospitalization duration. There was no difference in overall postsurgical complications, including anastomotic leak and abdominal abscess. Pouch formation markedly reduces the risk of dumping syndrome at 3 to 6 months [8.1% vs 32.4%; risk ratios (RR) 0.36, 95% CI, 0.21–0.60] and 12 to 24 months (2.8% vs 23.6%; RR 0.27, 95% CI, 0.16–0.46). The functional advantages of pouch reconstruction persist at 1 to 2 years, with aggregated data indicating considerably lower risks of esophagitis and heartburn (63% relative reduction), dumping syndrome (73% relative reduction), and food intake disturbance (50% relative reduction). At 12 to 24 months, albumin levels (40.5 vs 37.9 g/L; WMD 2.59, 95% CI, 1.35–3.84) and body mass index (22.2 vs 20.9 kg/m2; WMD 1.28, 95% CI, 0.61–1.94) are significantly higher among participants with a pouch.

Conclusions:

Pouch creation improves long-term functional and nutritional outcomes after total gastrectomy, without greater perioperative morbidity.
Ischemic Optic Neuropathy Secondary to Intravascular Lymphoma
Authors: Dinkin Marc , Lavi Ehud , Winterkorn Jacqueline , Oliveira Cristiano , Merkler Alexander E.
Published: October 2018

Background:

To describe a case of optic neuropathy associated with intravascular lymphoma (IVL).

Methods:

Case report and review of the literature.

Results:

A case of asymmetric binocular vision loss is described, preceded by transient vision loss. Associated optic perineural enhancement and enhancing and diffusion-positive cortical lesions were observed on magnetic resonance imaging. Biopsy of the cerebellum revealed exclusively intraluminal neoplastic B-cells consistent with IVL.

Conclusions:

Patients with IVL may rarely present with optic nerve involvement, presumably due to small vessel occlusion. The presentation may mimic features of anterior ischemic optic neuropathy including an acute onset and disc edema. Although optic nerve enhancement and associated white matter lesions may suggest optic neuritis, enhancement of the optic nerve sheath, as in this case, has a wide differential diagnosis, which includes giant cell arteritis. IVL should be considered in atypical cases of optic neuropathy accompanied by enhancing, diffusion-positive brain lesions that are not within a specific vascular territory.
Passive bristling of mako shark scales in reversing flows
Authors: Du Clos Kevin T. , Lang Amy , Devey Sean , Motta Philip J. , Habegger Maria Laura , Gemmell Brad J.
Published: October 2018

Shark skin has been shown to reduce drag in turbulent boundary layer flows, but the flow control mechanisms by which it does so are not well understood. Drag reduction has generally been attributed to static effects of scale surface morphology, but possible drag reduction effects of passive or active scale actuation, or ‘bristling’, have been recognized more recently. Here, we provide the first direct documentation of passive scale bristling due to reversing, turbulent boundary layer flows. We recorded and analysed high-speed videos of flow over the skin of a shortfin mako shark,Isurus oxyrinchus. These videos revealed rapid scale bristling events with mean durations of approximately 2 ms. Passive bristling occurred under flow conditions representative of cruise swimming speeds and was associated with two flow features. The first was a downward backflow that pushed a scale-up from below. The second was a vortex just upstream of the scale that created a negative pressure region, which pulled up a scale without requiring backflow. Both flow conditions initiated bristling at lower velocities than those required for a straight backflow. These results provide further support for the role of shark scale bristling in drag reduction.
Autonomously shaping natural climbing plants: a bio-hybrid approach
Authors: Wahby Mostafa , Heinrich Mary Katherine , Hofstadler Daniel Nicolas , Neufeld Ewald , Kuksin Igor , Zahadat Payam , Schmickl Thomas , Ayres Phil , Hamann Heiko
Published: October 2018

Plant growth is a self-organized process incorporating distributed sensing, internal communication and morphology dynamics. We develop a distributed mechatronic system that autonomously interacts with natural climbing plants, steering their behaviours to grow user-defined shapes and patterns. Investigating this bio-hybrid system paves the way towards the development of living adaptive structures and grown building components. In this new application domain, challenges include sensing, actuation and the combination of engineering methods and natural plants in the experimental set-up. By triggering behavioural responses in the plants through light spectra stimuli, we use static mechatronic nodes to grow climbing plants in a user-defined pattern at a two-dimensional plane. The experiments show successful growth over periods up to eight weeks. Results of the stimuli-guided experiments are substantially different from the control experiments. Key limitations are the number of repetitions performed and the scale of the systems tested. Recommended future research would investigate the use of similar bio-hybrids to connect construction elements and grow shapes of larger size.
Removal of toxic metals from aqueous solution by biochars derived from long-root
Eichhornia crassipes
Authors: Li Qiang , Tang Lizhou , Hu Jiang , Jiang Ming , Shi Xiaodong , Zhang Tianxi , Li Yuan , Pan Xuejun
Published: October 2018

Biochars were produced from long-root
Eichhornia crassipes
at four temperatures: 200, 300, 400 and 500°C, referred to as LEC200, LEC300, LEC400 and LEC500, respectively. The sorption ability of lead, zinc, copper and cadmium from aqueous solutions by four kinds of biochars was investigated. All the biochars had lower values of CEC and higher values of pH. LEC500 was the best one to bind toxic metals which can be reflected in the results of SEM, BET and elemental analyser. It was also found that alkyl, carboxyl, phosphate and cyano groups in the biochars can play a role in binding metals. In addition, the sorption processes of four metals by the biochars in different metal concentration were all excellently represented by the pseudo-second-order model with all correlation coefficients
R
2
> 0.95. And the sorption processes of four metals in different temperatures could be described satisfactorily by the Langmuir isotherms. According to calculated results by the Langmuir equation, the maximum removal capacities of Pb(II), Zn(II), Cu(II) and Cd(II) at 298 K were 39.09 mg g
−1
, 45.40 mg g
−1
, 48.20 mg g
−1
and 44.04 mg g
−1
, respectively. The positive value of the Δ
H
0
confirmed the adsorption process was endothermic and the negative value of Δ
G
0
confirmed the adsorption process was spontaneous. The sorption capacities were compared with several other lignocellulosic materials which implied the potential of long-root
Eichhornia crassipes
waste as an economic and excellent biosorbent for eliminating metal ions from contaminated waters.
The inflation of viscoelastic balloons and hollow viscera
Authors: De Pascalis Riccardo , Parnell William J. , Abrahams I. David , Shearer Tom , Daly Donna M. , Grundy David
Published: October 2018

For the first time, the problem of the inflation of a
nonlinear viscoelastic
thick-walled spherical shell is considered. Specifically, the wall has
quasilinear viscoelastic
constitutive behaviour, which is of fundamental importance in a wide range of applications, particularly in the context of biological systems such as hollow viscera, including the lungs and bladder. Experiments are performed to demonstrate the efficacy of the model in fitting relaxation tests associated with the volumetric inflation of
murine bladders
. While the associated
nonlinear elastic
problem of inflation of a balloon has been studied extensively, there is a paucity of studies considering the equivalent
nonlinear viscoelastic
case. We show that, in contrast to the elastic scenario, the peak pressure associated with the inflation of a neo-Hookean balloon is
not
independent of the shear modulus of the medium. Moreover, a novel numerical technique is described in order to solve the
nonlinear Volterra integral equation
in space and time originating from the fundamental problem of inflation and deflation of a thick-walled nonlinear viscoelastic shell under imposed pressure.
Recombinant infectious bronchitis viruses expressing heterologous S1 subunits: potential for a new generation of vaccines that replicate in Vero cells
Authors: Bickerton Erica , Dowgier Giulia , Britton Paul
Published: October 2018

The spike glycoprotein (S) of infectious bronchitis virus (IBV) comprises two subunits, S1 and S2. We have previously demonstrated that the S2 subunit of the avirulent Beau-R strain is responsible for its extended cellular tropism for Vero cells. Two recombinant infectious bronchitis viruses (rIBVs) have been generated; the immunogenic S1 subunit is derived from the IBV vaccine strain, H120, or the virulent field strain, QX, within the genetic background of Beau-R. The rIBVs BeauR-H120(S1) and BeauR-QX(S1) are capable of replicating in primary chicken kidney cell cultures and in Vero cells. These results demonstrate that rIBVs are able to express S1 subunits from genetically diverse strains of IBV, which will enable the rational design of a future generation of IBV vaccines that may be grown in Vero cells.
Use of Next Generation Sequencing to study two cowpox virus outbreaks
Authors: Antwerpen Markus H. , Georgi Enrico , Nikolic Alexandra , Zöller Gudrun , Wohlsein Peter , Baumgärtner Wolfgang , Peyrefitte Christophe , Charell Remi , Meyer Hermann
Published: October 2018

Background

Between 2008 and 2011 about 40 cases of human cowpox were reported from Germany and France. Infections had been acquired via close contact to infected, young pet rats. Sequencing of the hemagglutinin gene of various cowpox virus (CPXV) isolates resulted in an identical and unique sequence in each case pointing to a common source. In a second CPXV outbreak in cats in a small animal clinic in Germany in 2015, four out of five hospitalized cats showed identical hemagglutinin sequences and thus, a hospital-acquired transmission was assumed.

Methods

Homogenates of lesion material from rats, cats and humans were cultivated in cell culture. The genomes of 4 virus isolates, 9 CPXVs from our strain collections and from DNA of 3 paraffin-embedded lesion materials were determined by Next Generation Sequencing (NGS). For phylogenetic analyses a MAFFT-alignment was generated. A distance matrix based on concatenated SNPs was calculated and plotted as dendrogram using Unweighted Pair Group Method with Arithmetic mean (UPGMA) for visualization.

Results

Aligning of about 200.000 nucleotides of 8 virus isolates associated with the pet rat outbreak revealed complete identity of six genomes, the remainder two genomes differed in as little as 3 SNPs. When comparing this dataset with four already published CPXV genomes also associated with the pet rat outbreak, again a maximum difference of 3 SNPs was found. The outbreak which lasted from 2008 till 2011 was indeed caused by a single strain which has maintained an extremely high level of clonality over 4 years.

Aligning genomic sequences from 4 cases of feline cowpox revealed 3 identical sequences and one sequence which differed in 65 nucleotides. Although identical hemagglutinin sequences had been obtained from four hospitalized cats, genomic sequencing proved that a hospital-acquired transmission had occurred in only three cats.

Discussion

Analyzing the rather short sequence of the hemagglutinin gene is not sufficient to conduct molecular trace back analyses. Instead, whole genome sequencing is the method of choice which can even be applied to paraffin-embedded specimens.

Funding Statement

This publication was supported by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 653316.

This study was also supported in part by the European Union’s Horizon 2020 research and innovation program under grant agreement No 643476 (COMPARE).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Ecosystem tipping points in an evolving world
Authors: Dakos Vasilis , Matthews Blake , Hendry Andrew , Levine Jonathan , Loeuille Nicolas , Norberg Jon , Nosil Patrik , Scheffer Marten , Meester Luc De
Published: October 2018

There is growing concern over tipping points arising in ecosystems due to the crossing of environmental thresholds. Tipping points lead to strong and possibly irreversible shifts between alternative ecosystem states incurring high societal costs. Traits are central to the feedbacks that maintain alternative ecosystem states, as they govern the responses of populations to environmental change that could stabilize or destabilize ecosystem states. However, we know little about how evolutionary changes in trait distributions over time affect the occurrence of tipping points, and even less about how big scale ecological shifts reciprocally interact with trait dynamics. We argue that interactions between ecological and evolutionary processes should be taken into account for understanding the balance of feedbacks governing tipping points in nature.
Visual plasticity and exercise revisited: no evidence for a “cycling lane”
Authors: Finn Abigail E , Baldwin Alex S , Reynaud Alexandre , Hess Robert F
Published: October 2018

Experiments using enriched environments have shown that physical exercise modulates visual plasticity in rodents. A recent study (Lunghi & Sale, 2015, doi: 10.1016/j.cub.2015.10.026) investigated whether exercise also affects visual plasticity in adult humans. The plastic effect they measured was the shift in ocular dominance caused by 2 hours of monocular deprivation (e.g. by an eye patch). They used a binocular rivalry task to measure this shift. They found that the magnitude of the shift was increased by exercise during the deprivation period. This effect of exercise was later disputed by a study that used a different behavioural task (Zhouet al., 2017, doi: 10.1155/2017/4780876). Our goal was to determine whether the difference in task was responsible for that study’s failure to find an exercise effect. We set out to replicate Lunghi & Sale (2015). We measured ocular dominance with a rivalry task before and after 2 hours of deprivation. We measured data from two conditions in 30 subjects. On two separate days they either performed exercise or rested during the deprivation period. Contrary to the previous study, we find no significant effect of exercise. We hypothesise that exercise may affect rivalry dynamics in a way that interacts with the measurement of the deprivation effect.
Local vulnerability and global connectivity jointly shape neurodegenerative disease propagation
Authors: Zheng Ying-Qiu , Zhang Yu , Yau Yvonne , Zeighami Yahar , Larcher Kevin , Misic Bratislav , Dagher Alain
Published: October 2018

It is becoming increasingly clear that brain network organization shapes the course and expression of neurodegenerative diseases. Parkinson’s disease (PD) is marked by progressive spread of atrophy from the midbrain to subcortical structures and eventually, to the cerebral cortex. Recent discoveries suggest that the neurodegenerative process involves the misfolding and prion-like propagation of endogenous α-synuclein via axonal projections. However, the mechanisms that translate local “synucleinopathy” to large-scale network dysfunction and atrophy remain unknown. Here we use an agent-based epidemic spreading model to integrate structural connectivity, functional connectivity and gene expression, and to predict sequential volume loss due to neurodegeneration. The dynamic model replicates the spatial and temporal patterning of empirical atrophy in PD and implicates the substantia nigra as the disease epicenter. We reveal a significant role for both connectome topology and geometry in shaping the distribution of atrophy. The model also demonstrates that SNCA and GBA transcription influence α-synuclein concentration and local regional vulnerability. Functional co-activation further amplifies the course set by connectome architecture and gene expression. Altogether, these results support the theory that the progression of PD is a multifactorial process that depends on both cell-to-cell spreading of misfolded proteins and regional vulnerability.
Prediction of Algal Blooms in the Great Lakes through a Convolution Neural Network of Remote Sensing Data
Authors: Srinivasan Karthik , Duvvur Vikram , Hess Daniel
Published: October 2018

Harmful algal blooms (HABs) are the proliferation of algae due to eutrophication and have severe repercussions to the ecological balance in many water bodies, due to the toxins the algae produce. Additionally, the identification and prediction of these HABs has been a challenge in the scientific community due to the interactions between both biological and physical processes that cause the HABs. Here, we used remote sensing data to bypass these issues; remote sensing data provides significant information about the coverage of chlorophyll which can be used to locate HABs. Using this indicator of HABs, we trained a Convolution Neural Network (CNN) to identify nine types of algal blooms, using 25 epochs of 900 images, which can predict algal bloom shapes with an 80 percent accuracy. This approach of HAB identification can easily be applied to other aquatic ecosystems where remote sensing data is present.
The global diversity of the major parasitic nematodeHaemonchus contortusis shaped by human intervention and climate
Authors: Sallé G. , Doyle S.R. , Cortet J. , Cabaret J. , Berriman M. , Holroyd N. , Cotton J.A
Published: October 2018

The gastrointestinal parasiteHaemonchus contortusis an haematophagous parasitic nematode of veterinary interest and a model for the study of drug resistance mechanisms or host-parasite interactions. To understand its evolutionary history, and its ability to adapt in the face of climatic and drug pressure, we have performed an extensive survey of genome-wide diversity using single-worm whole genome sequencing of 223 individuals sampled from 19 isolates spanning five continents. The pattern of global diversity is driven by an African origin for the species, together with contemporary dispersal that is consistent with modern human movement, with evidence for parasites spreading during the transatlantic slave trade and colonisation of Australia presented. Strong selective sweeps were identified in independent populations each surrounding the β-tubulin locus, a target of benzimidazole anthelmintic drug treatment used widely to controlH. contortusinfections. These signatures of selection were further supported by signals of diversifying selection enriched in genes involved in response to drugs, as well as other anthelmintic-associated biological functions including pharyngeal pumping and oviposition. From these analyses, we identify some known, and previously undescribed, candidate genes that may play a role in ivermectin resistance. Finally, we describe genetic signatures of climate-driven adaptation, revealing a gene acting as an epigenetic regulator and components of thedauerpathway may play a role in adaptation in the face of climatic fluctuations. These results begin to define genetic adaptation to climate for the first time in a parasitic nematode, and provides insight into the ongoing expansion in the range ofHaemonchus contortus, which may have consequences for the management of this parasite.
Single nucleotide polymorphisms of the c-MYC gene’s relationship with formation of Burkitt’s lymphoma using bioinformatics analysis
Authors: Sati Anfal Osama Mohamed , Osman Weaam Anwer , Ahmedon Enas Abdalla Mohammed , Yousif Safa Hamed Elneel , Khairi Enas Dawoud , Hassan Alaa Ibrahim Mohammed , Elsammani Moshtaha Ali Ibrahim , Salih Mohamed Ahmed
Published: October 2018

Burkitt’s lymphoma (BL) is an aggressive form of non-Hodgkin lymphoma, originates from germinal center B cells, MYC gene (MIM ID 190080) is an important proto-oncogene transcriptional factor encoding a nuclear phosphoprotein for central cellular processes. Dysregulated expression or function of c-MYC is one of the most common abnormalities in BL. This study focused on the investigation of the possible role of single nucleotide polymorphisms (SNPs) in MYC gene associated with formation of BL.

MYC SNPs were obtained from NCBI database. SNPs in the coding region that are non-synonymous (nsSNPs) were analysed by multiple programs such as SIFT, Polyphen2, SNPs&GO, PHD-SNP and I-mutant. In this study, a total of 286 Homo sapiens SNPs were found. Roughly, forty-eight of them were deleterious and were furtherly investigated.

Eight SNPs were considered most disease causing [rs4645959 (N26S), rs4645959 (N25S), rs141095253 (P396L), rs141095253 (P397L), rs150308400 (C233Y), rs150308400 (C147Y), rs150308400 (C147Y), rs150308400 (C148Y)] according to the four softwares used. Two of which have not been reported previously [rs4645959 (N25S), rs141095253 (P396L)]. SNPs analysis helps is a diagnostic marker which helps in diagnosing and consequently, finding therapeutics for clinical diseases. This is through SNPs genotyping arrays and other techniques. Thus, it is highly recommended to confirm the findings in this study in vivo and in vitro.
Antigen-specific T-cell receptor signatures of cytomegalovirus infection
Authors: Huth Alina , Liang Xiaoling , Krebs Stefan , Blum Helmut , Moosmann Andreas
Published: October 2018

Cytomegalovirus (CMV) is a prevalent human pathogen. The virus cannot be eliminated from the body, but is kept in check by CMV-specific T cells. Patients with an insufficient T-cell response, such as transplant recipients, are at high risk of developing CMV disease. However, the CMV-specific T-cell repertoire is complex, and is not yet clear which T cells protect best against virus reactivation and disease. Here we present a highly resolved characterization of CMV-specific CD8+ T cells based on enrichment by specific peptide stimulation and mRNA sequencing of their T-cell receptor β chains (TCRβ). Our analysis included recently identified T-cell epitopes restricted through HLA-C, whose presentation is resistant to viral immunomodulation, and well-studied HLA-B-restricted epitopes. In 8 healthy virus carriers, we identified a total of 1052 CMV-specific TCRβ chains. HLA-C-restricted, CMV-specific TCRβ clonotypes theex vivoT-cell response, and contributed the highest-frequency clonotype of the entire repertoire in 2 of 8 donors. We analyzed sharing and similarity of CMV-specific TCRβ sequences and identified 63 public or related sequences belonging to 17 public TCRβ families. In our cohort and in an independent cohort of 352 donors, the cumulative frequency of these public TCRβ family members was a highly discriminatory indicator of carrying both CMV infection and the relevant HLA type. Based on these findings, we propose CMV-specific TCRβ signatures as a biomarker for an antiviral T-cell response to identify patients in need of treatment and to guide future development of immunotherapy.
AGEpy: a Python package for computational biology
Authors: Metge Franziska , Sehlke Robert , Boucas Jorge
Published: October 2018

AGEpy is a Python package focused on the transformation of interpretable data into biological meaning. It is designed to support high-throughput analysis of pre-processed biological data using either local Python based processing or Python based API calls to local or remote servers. In this application note we describe its different Python modules as well as its command line accessible toolsaDiff,abed,blasto,david, andobo2tsv.

Availability:

The open source AGEpy Python package is freely available at:https://github.com/mpg-age-bioinformatics/AGEpy.

Contact:

jorge.boucas@age.mpg.de
Organ-wide and ploidy-dependent regulations both contribute to cell size determination: evidence from a computational model of tomato fruit
Authors: Baldazzi Valentina , Valsesia Pierre , Genard Michel , Bertin Nadia
Published: October 2018

The development of a new organ is the result of coordinated events of cell division and expansion, in strong interaction with each other. This paper presents a dynamic model of tomato fruit development that includes cell division, endoreduplication and expansion processes. The model is used to investigate the potential interaction among these developmental processes, in the perspective of the neo-cellular theory. In particular, different control schemes (either cell-autonomous or organ-controlled) are tested and compared to experimental data related to two contrasted genotypes. The model shows that a pure cell-autonomous control fails to reproduce the observed cell size distribution, and an organ-wide control is required in order to get realistic cell size variations. The model also supports the role of endoreduplication as an important determinant of final cell size and suggests that a direct effect of endoreduplication on cell expansion is needed in order to obtain a significant correlation between size and ploidy, as observed in real data.
Silencing cathepsin L expression reduces Myzus persicae protein content and the nutritional value as prey for Coccinella septempunctata
Authors: Rauf Imran , Asif Muhammad , Amin Imran , Naqvi Rubab Zahra , Umer Noroza , Mansoor Shahid , Jander Georg
Published: October 2018

Gut-expressed aphid genes, which may be more easily inhibited by RNA interference (RNAi) constructs, are attractive targets for pest control efforts involving transgenic plants. Here we show that expression of cathepsin L, a cysteine protease that functions in aphid guts, can be reduced by expression of an RNAi construct in transgenic tobacco. The effectiveness of this approach is demonstrated by up to 80% adult mortality, reduced fecundity, and delayed nymph production of Myzus persicae (green peach aphids) when cathepsin L expression was reduced by plant-mediated RNAi. Consistent with the function of cathepsin L as a gut protease, M. persicae fed on the RNAi plants had a lower protein content in their bodies and excreted more protein in their honeydew. Larvae of Coccinella septempunctata (seven-spotted ladybugs) grew more slowly on aphids having reduced cathepsin L expression, suggesting that prey insect nutritive value, and not just direct negative effects of the RNAi construct, needs to be considered when producing transgenic plants for RNAi-mediated pest control.

Highlights

Silencing expression of cathepsin L by RNA interference reduces protein content of Myzus persicae (green peach aphid) bodies.

Honeydew of aphids with cathepsin L silenced contains elevated protein.

Cathepsin L is required for efficient protein uptake from phloem sap.

Aphids with cathepsin L expression silenced have increased mortality and fewer offspring.

Coccinella septempunctata (seven-spotted ladybugs) grow more slowly on aphids with expression of cathepsin L silenced.
CFP-1 interacts with HDAC1/2 complexes inC. elegansdevelopment
Authors: Pokhrel Bharat , Chen Yannic , Biro Jonathan Joseph
Published: October 2018

CFP-1 (CXXC finger binding protein 1) is an evolutionarily conserved protein that binds to non-methylated CpG-rich promoters in humans andC. elegans. This conserved epigenetic regulator is a part of the COMPASS complex that contains the H3K4me3 methyltransferase SET1 in mammals and SET-2 inC. elegans. Previous studies have indicated the importance ofcfp-1in embryonic stem cell differentiation and cell fate specification. However, neither the function nor the mechanism of action ofcfp-1is well understood at the organismal level. To further investigate the function of CFP-1, we have characterisedC. elegansCOMPASS mutantscfp-1(tm6369)andset-2(bn129). We found that bothcfp-1andset-2play an important role in the regulation of fertility and development of the organism. Furthermore, we found that bothcfp-1andset-2are required for H3K4 trimethylation and play a repressive role in the expression of heat shock and salt-inducible genes. Interestingly, we found thatcfp-1but notset-2genetically interacts with Histone Deacetylase (HDAC1/2) complexes to regulate fertility, suggesting a function of CFP-1 outside of the COMPASS complex. Additionally we found thatcfp-1andset-2acts on a separate pathways to regulate fertility and development ofC. elegans. Our results suggest that CFP-1 genetically interacts with HDAC1/2 complexes to regulate fertility, independent of its function within COMPASS complex. We propose that CFP-1 could cooperate with COMPASS complex and/or HDAC1/2 in a context dependent manner.
Self-Organized Critical Control of Genome Expression: Novel Scenario on Cell-Fate Decision
Authors: Tsuchiya Masa , Giuliani Alessandro , Yoshikawa Kenichi
Published: October 2018

In our current studies on whole genome expression in several biological processes, we have demonstrated the actual existence of self-organized critical control (SOC) of gene expression at both population and single cell level. SOC allows for cell-fate change by critical transition encompassing the entire genome expression that, in turn, is partitioned into distinct response domains (critical states).

In this paper, we go more in depth into the elucidation of SOC control of genome expression focusing on the determination of critical point (CP) and associated distinct critical states in single-cell genome expression. This leads us to the proposal of a potential universal model with genome-engine mechanism for cell-fate change. Our findings suggest that the CP is fixed point in terms of temporal expression variance, where the CP (set of critical genes) becomes active (ON) for cell-fate change (‘super-critical’ in genome-state) or else inactive (OFF) state (‘sub-critical’ in genome-state); this may lead to a novel scenario of the cell-fate control through activating or inactivating CP.
Somatic Evolution Introduces Distinctive Changes in Proteome Composition in Cancer Types
Authors: Tsuber Viktoriia
Published: October 2018

On the proteome level, somatic evolution in cancer is asymmetric, with several amino acids being irreversibly lost and the others gained across cancer types. However, though the gains and losses of amino acids are consistent in multiple cancer types, their magnitudes and prevalences differ. Here, we analyzed data on circa three million amino acid substitutions in the Catalogue of Somatic Mutations in Cancer (COSMIC) database to investigate profiles of gains and losses of amino acids in 23 human cancer types. We found characteristic differences in amino acid gain/loss profiles in the cancer types, with several of them demonstrating very specific profiles of proteome alterations associated with distinct endogenous or exogenous factors.
Sendai Virus Infection Induces Expression of Novel RNAs in Human Cells
Authors: Mandhana Roli , Horvath Curt M.
Published: October 2018

Innate antiviral immune responses are driven by virus-induced changes in host gene expression. While much research on antiviral effectors has focused on virus-inducible mRNAs, recent genome-wide analyses have identified hundreds of novel target sites for virus-inducible transcription factors and RNA polymerase. These sites are beyond the known antiviral gene repertoire and their contribution to innate immune responses is largely unknown. In this study, RNA-sequencing of mock-infected and Sendai virus-infected cells was performed to characterize the virus-inducible transcriptome and identify novel virus-inducible RNAs (nviRNAs). Virus-inducible transcription was observed throughout the genome resulting in expression of 1755 previously RefSeq-annotated RNAs and 1545 nviRNAs. The previously-annotated RNAs primarily consist of protein-coding mRNAs, including several well-known antiviral mRNAs that had low sequence conservation but were highly virus-inducible. The previously-unannotated nviRNAs were mostly noncoding RNAs with poor sequence conservation. Independent analyses of nviRNAs based on infection with Sendai virus, influenza virus, and herpes simplex virus 1, or direct stimulation with IFNα revealed a range of expression patterns in various human cell lines. These phylogenetic and expression analyses suggest that many of the nviRNAs share the high inducibility and low sequence conservation characteristic of well-known primary antiviral effectors and may represent dynamically evolving antiviral factors.
Genetic characterization of chytrids isolated from larval amphibians collected in central and east Texas
Authors: Marshall Thomas L. , Baca Carlos R. , Correa Decio T. , Forstner Michael R. J. , Hahn Dittmar , Rodriguez David
Published: October 2018

Chytridiomycosis, an emerging infectious disease caused by the fungal pathogenBatrachochytrium dendrobatidis(Bd), has caused amphibian population declines worldwide.Bdwas first described in the 1990s and there are still geographic gaps in the genetic analysis of this globally distributed pathogen. Relatively few genetic studies have focused on regions whereBdexhibits low virulence, potentially creating a bias in our current knowledge of the pathogen’s genetic diversity. Disease-associated declines have not been recorded in Texas (USA), yetBdhas been detected on amphibians in the state. These strains have not been isolated and characterized genetically; therefore, we isolated, cultured, and genotypedBdfrom central Texas and compared isolates to a panel of previously genotyped strains distributed across the Western Hemisphere. We also isolated other chytrids not known to infect amphibians from east Texas. To identify larval amphibian hosts, we sequenced part of the COI gene. Among 37Bdisolates from Texas, we detected 19 unique multi-locus genotypes, but found no genetic structure associated with host species, Texas localities, or across North America. Isolates from central Texas exhibit high diversity and genetically cluster withBd-GPL isolates from the western U.S. that have caused amphibian population declines. This study genetically characterizes isolates ofBdfrom the south central U.S. and adds to the global knowledge ofBdgenotypes.
The impact of data reduction and lossy image formats on electron microscope images
Authors: Eng Edward T. , Kopylov Mykhailo , Negro Carl J. , Dallaykan Sarkis , Rice William J. , Jordan Kelsey D. , Kelley Kotaro , Carragher Bridget , Potter Clinton S.
Published: October 2018

Recent advances in instrumentation and software for cryoEM have increased the applicability and utility of this method. Coupled with the adoption of automated pipelines, significant infrastructure support is required to sustain high throughput workflows. In particular, data generation rates may outpace the ability to deploy data storage and archival solutions. We have investigated what effects data compression and conversion to different file formats have on the ability to obtain high resolution cryoEM reconstructions. Standard lossless data compression strategies have a high impact on reducing the size of direct detector electron counting movie stacks, but provide more modest gains for aligned summed images. We show that EM images can be compressed using standard lossy methods to reduce file storage to 5–10% of the size of the original aligned sum or movie stack file and yet still retain enough information such that modern image processing pipelines will provide sub-2Å reconstructions from the compressed data.