bluuebunny/crossref_metadata_2025 huggingface dataset:
Sumo Puff: Tidal debris or disturbed ultra-diffuse galaxy?
Authors: Greco Johnny P , Greene Jenny E , Price-Whelan Adrian M , Leauthaud Alexie , Huang Song , Goulding Andy D , Strauss Michael A , Komiyama Yutaka , Lupton Robert H , Miyazaki Satoshi , Takada Masahiro , Tanaka Masayuki , Usuda Tomonori
Published: June 2017

We report the discovery of a diffuse stellar cloud with an angular extent ≳30″, which we term “Sumo Puff”, in data from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP). While we do not have a redshift for this object, it is in close angular proximity to a post-merger galaxy at redshift z = 0.0431 and is projected within a few virial radii (assuming similar redshifts) of two other ∼L⋆ galaxies, which we use to bracket a potential redshift range of 0.0055 < z < 0.0431. The object’s light distribution is flat, as characterized by a low Sérsic index (n ∼ 0.3). It has a low central g-band surface brightness of ∼26.4 mag arcsec−2, large effective radius of ∼13″ (∼11 kpc at z = 0.0431 and ∼1.5 kpc at z = 0.0055), and an elongated morphology (b/a ∼ 0.4). Its red color (g − i ∼ 1) is consistent with a passively evolving stellar population and similar to the nearby post-merger galaxy, and we may see tidal material connecting Sumo Puff with this galaxy. We offer two possible interpretations for the nature of this object: (1) it is an extreme, galaxy-sized tidal feature associated with a recent merger event, or (2) it is a foreground dwarf galaxy with properties consistent with a quenched, disturbed, ultra-diffuse galaxy. We present a qualitative comparison with simulations that demonstrates the feasibility of forming a structure similar to this object in a merger event. Follow-up spectroscopy and/or deeper imaging to confirm the presence of the bridge of tidal material will be necessary to reveal the true nature of this object.
Can Recurrence After an Acute Episode of Low Back Pain Be Predicted?
Authors: Machado Gustavo C. , Maher Chris G. , Ferreira Paulo H. , Latimer Jane , Koes Bart W. , Steffens Daniel , Ferreira Manuela L.
Published: June 2017

Background

Although recurrence is common after an acute episode of low back pain, estimates of recurrence rates vary widely and predictors of recurrence remain largely unknown.

Objective

The purposes of the study were to determine the 1-year incidence of recurrence in participants who recovered from an acute episode of low back pain and to identify predictors of recurrence.

Design

The design was an inception cohort study nested in a case-crossover study.

Methods

For 12 months, 832 of the 999 participants who initially presented to primary care within the first 7 days of an episode of low back pain were followed. Of these participants, 469 recovered (1 month pain free) from the index episode within 6 weeks and were included in this study. Recurrence was defined as a new episode lasting more than 1 day, or as an episode of care seeking. Putative predictors were assessed at baseline and chosen a priori. Multivariable regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results

The 1-year incidence of recurrence of low back pain was 33%, and the 1-year incidence of recurrence of low back pain with care seeking was 18%. Participants reporting more than 2 previous episodes of low back pain had increased odds of future recurrences (OR = 3.18, CI = 2.11–4.78). This factor was also associated with recurrent episodes that led to care seeking (OR = 2.87, CI = 1.73–4.78). No other factors were associated with recurrences.

Limitations

There are limitations inherent in reliance on recall.

Conclusions

After an acute episode of low back pain, one-third of patients will experience a recurrent episode, and approximately half of those will seek care. Experiencing more than 2 previous episodes of low back pain triples the odds of a recurrence within 1 year.
Should Hyperoxia Be Avoided During Sepsis? An Experimental Study in Ovine Peritonitis*
Authors: He Xinrong , Su Fuhong , Xie Keliang , Taccone Fabio Silvio , Donadello Katia , Vincent Jean-Louis
Published: June 2017

Objectives:

Optimizing oxygen delivery is an important part of the hemodynamic resuscitation of septic shock, but concerns have been raised over the potentially deleterious effects of hyperoxia. We evaluated the impact of hyperoxia on hemodynamics, the microcirculation, and cerebral and renal metabolism in an ovine model of septic shock.

Design:

Randomized animal study.

Setting:

University hospital animal research laboratory.

Subjects:

Fourteen adult female sheep.

Interventions:

After induction of fecal peritonitis, sheep were randomized to ventilation with an Fio
2 of 100% (n = 7) or an Fio
2 adjusted to maintain Pao
2 between 90 and 120 mm Hg (n = 7, control). All animals were fluid resuscitated and observed until death.

Measurements and Main Results:

In addition to hemodynamic measurements, we assessed the sublingual microcirculation, renal and cerebral microdialysis and microvascular perfusion, and brain tissue oxygen pressure. Hyperoxic animals initially had a higher mean arterial pressure than control animals. After onset of shock, hyperoxia blunted the decrease in stroke volume index observed in the control group. Hyperoxia was associated with a higher sublingual microcirculatory flow over time, with higher cerebral perfusion and brain tissue oxygen pressure and with a lower cerebral lactate-to-pyruvate ratio than in control animals. Hyperoxia was also associated with preserved renal microvascular perfusion, lower renal lactate-to-pyruvate ratio, and higher Pao
2/Fio
2 ratio.

Conclusions:

In this acute peritonitis model, hyperoxia induced during resuscitation provided better hemodynamics and peripheral microvascular flow and better preserved cerebral metabolism, renal function, and gas exchange. These observations are reassuring with recent concerns about excessive oxygen therapy in acute diseases.
Service line structure and decision-maker attention in three health systems: Implications for patient-centered care
Authors: Louis Christopher J. , Clark Jonathan R. , Gray Barbara , Brannon Diane , Parker Victoria
Published: June 2017

Background:

Scholars have noted a disconnect between the level at which structure is typically examined (the organization) and the level at which the relevant coordination takes place (service delivery). Accordingly, our understanding of the role structure plays in care coordination is limited.

Purpose:

In this article, we explore service line structure, with an aim of advancing our understanding of the role service line structure plays in producing coordinated, patient-centered care. We do so by giving special attention to the cognitive roots of patient-centeredness.

Methodology/Approach:

Our exploratory study relied on comparative case studies of the breast cancer service lines in three health systems. Nonprobability discriminative snowball sampling was used to identify the final sample of key informants. We employed a grounded approach to analyzing and interpreting the data.

Results:

We found substantial variation across the three service lines in terms of their structure. We also found corresponding variation across the three case sites in terms of where informant attention was primarily focused in the process of coordinating care. Drawing on the attention-based view of the firm, our results draw a clear connection between structural characteristics and the dominant focus of attention (operational tactics, provider roles and relationships, or patient needs and engagement) in health care service lines.

Conclusion:

Our exploratory results suggest that service line structures influence attention in two ways: (a) by regulating the type and intensity of the problems facing service line participants and (b) by encouraging (or discouraging) a shared purpose around patient needs.

Practice Implications:

Patient-centered attention—a precursor to coordinated, patient-centered care—depends on the internal choices organizations make around service line structure. Moreover, a key task for organizational and service line leaders is to structure service lines to create a context that minimizes distractions and enables care providers to focus their attention on the needs of their patients.
Descemet's Membrane Dehiscence Resulting From Misdirected Viscoelastic During Anterior Chamber Reformation
Authors: Chay Edward , Dastgir Ghulam , Scott Wayne , Lazzaro Douglas
Published: June 2017

We report a case of Descemet's membrane detachment after inadvertent intrastromal injection of hyaluronic acid. Surgical removal was attempted with minimal but slow improvement. Near-complete resolution occurred with subsequent conservative management within 6 weeks.
Reflective practice in health care and how to reflect effectively
Authors: Koshy Kiron , Limb Christopher , Gundogan Buket , Whitehurst Katharine , Jafree Daniyal J.
Published: June 2017

Reflective practice is a paper requirement of your career progression in health care. However, if done properly, it can greatly improve your skills as a health care provider. This article provides some structure to reflective practice to allow a health care provider to engage more with reflective practice and get more out of the experience.
Liver Abscess in Patients With Leukemia and Prolonged Neutropenia
Authors: Grabau Michael , Pandya Shuchi , Nanjappa Sowmya , Shenoy Rahul , Aslam Sadaf , Greene John N.
Published: June 2017

Patients with leukemia are at a high risk of developing disseminated invasive fungal and/or bacterial infections due to prolonged neutropenia, which is usually caused by myelosuppressive chemotherapy. Disseminated fungal infections in the setting of prolonged neutropenia result in high mortality. The most effective means to improve patient outcome is early diagnosis and treatment when preventive measures have failed. The most common fungal pathogens are Candida spp and Aspergillus spp. Rare causes of such infection are by Mucor and Entomopthorales spp, Fusarium spp, and Scedosporium spp, each having unique epidemiology, pathophysiology, and treatment options. We present a case of disseminated hepatic, pulmonary, bowel, and appendix mucormycosis successfully treated with antifungal therapy and without surgical intervention. We also review the literature regarding hepatic abscesses and disseminated invasive fungal infections along with current treatment strategies for Mucor infections.
Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia—a controlled pilot-study
Authors: Ciampi de Andrade Daniel , Maschietto Mariana , Galhardoni Ricardo , Gouveia Gisele , Chile Thais , Victorino Krepischi Ana C. , Dale Camila S. , Brunoni André R. , Parravano Daniella C. , Cueva Moscoso Ana S. , Raicher Irina , Kaziyama Helena H. S. , Teixeira Manoel J. , Brentani Helena P.
Published: June 2017

To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the Illumina-HumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n = 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene–gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of genes was enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.
An Optimal Scheduling for Medical Equipment Preventive Maintenance Over a Finite Planning Horizon Using Ant Colony Algorithm
Authors: Saleh Neven , Rosati Samanta , Sharawi Amr , Wahed Manal Abdel , Balestra Gabriella
Published: June 2017

The importance of preventive maintenance management has been gradually recognized specially with the great attention to the role of health technology management. Finding the optimal schedule to perform preventive maintenance for medical equipment is rarely considered in the literature. This research suggests using ant colony optimization method to solve the problem of finding the optimal preventive maintenance schedule. We developed 2 versions of the algorithm, both starting from a prioritized medical equipment list and differing in the heuristic function. The experimental results indicate the effectiveness of the ant colony optimization algorithm for this kind of problems.
Bryukhonenko’s Autojector: The First Apparatus for Cardiopulmonary Bypass and Extracorporeal Life Support
Authors: Glyantsev Sergey P. , Bogopolsky Pavel M. , Tchantchaleishvili Vakhtang
Published: June 2017

Sergey Bryukhonenko was a prominent Soviet physician-scientist who from 1922 to 1924 developed a methodology for perfusing a canine head and keeping it alive using the first extracorporeal life support device he created called “Autojector.” From 1926 to 1927, in collaboration with surgeon Nikolay Terebinsky, he performed a series of perfusion experiments of the entire canine body using a more advanced model of Autojector. Subsequently, Bryukhonenko concluded the possibility of extending this methodology to heart surgery. Although Bryukhonenko never applied his device in clinical practice, Terebinsky used the concept from 1929 to 1940 on open heart experiments. Although he never received sufficient acknowledgement for his pioneering work, it must be recognized that Bryukhonenko, along with Terebinsky, laid the groundwork for developing cardiac surgery in the Soviet Union.
A Prospective Study of Loose Tissue Fragments in Non–Small Cell Lung Cancer Resection Specimens
Authors: Blaauwgeers Hans , Flieder Douglas , Warth Arne , Harms Alexander , Monkhorst Kim , Witte Birgit , Thunnissen Erik
Published: June 2017

The World Health Organization Classification of Lung Tumors considers “Spread Through Air Spaces” a form of invasion in lung adenocarcinoma. The recently described spread of free-floating cell clusters during lung specimen sectioning, otherwise known as “Spread Through A Knife Surface,” represents an ex vivo artifact. The purpose of this study was to prospectively investigate the presence and frequency of these free-floating tumor cell clusters in surgically resected lung cancer specimens and their possible relation to gross examination procedures. A prospective, multi-institutional study of non–small cell lung cancer resection specimen was undertaken. At prosection the first cut was made with a clean knife; the second cut was made in a parallel plane to the first. Four tissue blocks were taken from upper and lower parts of first and second cuts. Hematoxylin and eosin–stained slides were examined for displaced benign and/or malignant tissue fragments. Forty-four resection specimens were studied. The mean number of tumor clusters for blocks 1 to 4 was 0.36, 1.44, 1.86, and 1.95, respectively, and for benign fragments was 0.11, 0.11, 0.13, and 0.25, respectively. Almost all cell clusters were intra-alveolar. Comparison of tumor cell clusters in block 1 with blocks 2 to 4 was significant with P-values (Friedman test for repeated measures 0.03) 0.031, 0.02, and 0.05, respectively. Overall 93% of the loose tissue fragments could be explained by mechanical forces associated with tissue handling. While the 2015 World Health Organization Classification of Lung Tumors recognizes Spread Through Air Spaces as a form of lung cancer invasion, such is debatable and in many instances likely represents mechanical artifact, including dissemination along the prosecting knife blade.
Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
Authors: Hardell Elin , Josefson Sofia , Ghaderi Mehran , Skeie-Jensen Tone , Westbom-Fremer Sofia , Cheek Elizabeth H. , Bell Debra , Selling Jonas , Schoolmeester John K. , Måsbäck Anna , Davidson Ben , Carlson Joseph W.
Published: June 2017

Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm2) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.
Soft-Tissue Reconstruction of Large Spinal Defects: A 12-Year Institutional Experience
Authors: Devulapalli Chris , Broyles Justin M. , Bello Ricardo , Elgendy Tarek , Yalanis Georgia , Redett Richard , Rosson Gedge D. , Sacks Justin M.
Published: June 2017

Background:

Spinal resections can lead to defects requiring soft-tissue reconstruction. The purpose of this study was to review the authors’ institutional experience with reconstruction of spinal defects and identify risk factors predictive of wound complications, focusing on timing of reconstruction with ablative surgery.

Methods:

The authors retrospectively reviewed patients who underwent spinal resection and required soft-tissue reconstruction from 2002 to 2014. Logistic regression was performed to identify risk factors for complications.

Results:

Of 289 reconstructions performed in 259 patients, 64 cases (22.1 percent) had major wound complications requiring reoperation. Lumbosacral defects were the most common location (43.6 percent) and paraspinous muscle flaps were the preferred reconstructive method used for all defect regions. A total of 224 reconstructions (77.5 percent) were performed immediately at the time of spinal surgery, and 65 (22.5 percent) were performed in delayed fashion as a result of wound complications from previous spinal surgery. Patients undergoing immediate reconstruction had significantly lower rates of instrumentation removal (0.9 percent versus 4.6 percent; p = 0.043), unplanned reoperations (0.5 versus 1.3; p < 0.001), and mortality (0.9 percent versus 9.2 percent; p < 0.001) compared with those undergoing delayed reconstruction. On logistic regression analysis, presence of instrumentation (OR, 3.2; p = 0.012), requirement for a free flap (OR, 9.0; p = 0.016), and spinal cord exposure (OR, 2.6; p = 0.036) were associated with increased odds of a major wound complication.

Conclusion:

Spinal resections carry significant surgical-site morbidity, and selection of high-risk patients for immediate reconstruction with locoregional muscle flaps may be beneficial for improving wound-related outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Three-Dimensional Cone Beam Computed Tomography Volumetric Outcomes of rhBMP-2/Demineralized Bone Matrix versus Iliac Crest Bone Graft for Alveolar Cleft Reconstruction
Authors: Liang Fan , Yen Stephen L-K. , Imahiyerobo Thomas , Sanborn Luke , Yen Leia , Yen Daniel , Nazarian Sheila , Jedrzejewski Breanna , Urata Mark , Hammoudeh Jeffrey
Published: June 2017

Background:

Recent studies indicate that recombinant human bone morphogenetic protein-2 (rhBMP-2) in a demineralized bone matrix scaffold is a comparable alternative to iliac bone autograft in the setting of secondary alveolar cleft repair. Postreconstruction occlusal radiographs demonstrate improved bone stock when rhBMP-2/demineralized bone matrix (DBM) scaffold is used but lack the capacity to evaluate bone growth in three dimensions. This study uses cone beam computed tomography to provide the first clinical evaluation of volumetric and density comparisons between these two treatment modalities.

Methods:

A prospective study was conducted with 31 patients and 36 repairs of the alveolar cleft over a 2-year period. Twenty-one repairs used rhBMP-2/DBM scaffold and 14 repairs used iliac bone grafting. Postoperatively, occlusal radiographs were obtained at 3 months to evaluate bone fill; cone beam computed tomographic images were obtained at 6 to 9 months to compare volumetric and density data.

Results:

At 3 months, postoperative occlusal radiographs demonstrated that 67 percent of patients receiving rhBMP-2/DBM scaffold had complete bone fill of the alveolus, versus 56 percent of patients in the autologous group. In contrast, cone beam computed tomographic data showed 31.6 percent (95 percent CI, 24.2 to 38.5 percent) fill in the rhBMP-2 group compared with 32.5 percent (95 percent CI, 22.1 to 42.9 percent) in the autologous population. Density analysis demonstrated identical average values between the groups (1.38 g/cc).

Conclusions:

These data demonstrate comparable bone regrowth and density values following secondary alveolar cleft repair using rhBMP-2/DBM scaffold versus autologous iliac bone graft. Cone beam computed tomography provides a more nuanced understanding of true bone regeneration within the alveolar cleft that may contribute to the information provided by occlusal radiographs alone.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML
Authors: Gore Lia , Triche Timothy J. , Farrar Jason E. , Wai Daniel , Legendre Christophe , C Gooden Gerald , Liang Winnie S. , Carpten John , Lee David , Alvaro Frank , Macy Margaret E. , Arndt Carola , Barnette Philip , Cooper Todd , Martin Laura , Narendran Aru , Pollard Jessica , Meshinchi Soheil , Boklan Jessica , Arceci Robert J , Salhia Bodour
Published: June 2017

Background

Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints.

Results

Twenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A, 14 in Arm B). All patients experienced neutropenia and thrombocytopenia. The most common grade 3 and 4 non-hematologic adverse events observed were gastrointestinal toxicities and hypophosphatemia. Plasma decitabine PK were similar to previously reported adult data. Overall CR/CRi was similar for the two arms. MRD negativity at end-induction was 85% in Arm A versus 67% in Arm B patients. DNA methylation measured in peripheral blood over the course of treatment tracked with blast clearance and matched marrow aspirates at day 0 and day 21. Unlike end-point marrow analyses, promoter methylation in blood identified an apparent reversal of response in the lone treatment failure, one week prior to the patient’s marrow aspirate confirming non-response. Decitabine-induced effects of end-induction marrows in Arm A were reflected by changes in DNA methylation and gene expression comparison with matched paired marrow diagnostic aspirates.

Conclusions

This first-in-pediatrics trial demonstrates that decitabine prior to standard combination chemotherapy is feasible and well tolerated in children with newly diagnosed AML. Pre-treatment with decitabine may represent a newer therapeutic option for pediatric AML, especially as it appears to induce important epigenetic alterations. The novel biological correlates studied in this trial offer a clinically relevant window into disease progression and remission. Additional studies are needed to definitively assess whether decitabine can enhance durability responses in children with AML. This trial was registered atwww.clinicaltrials.govasNCT01177540.
On the relative role of different age groups during influenza A epidemics in Germany, 2002-2017
Authors: Goldstein Edward
Published: June 2017

Background

There is limited information about the role of different age groups, particularly subgroups of school-age children and younger adults in propagating influenza epidemics.

Methods

For a communicable disease outbreak, some subpopulations may play a disproportionate role during the ascent of the outbreak due to increased susceptibility and/or contact rates. Such subpopulations can be identified by considering the proportion that cases in a subpopulation represent among all cases in the population occurring before the epidemic peak (Bp), the corresponding proportion after the epidemic peak (Ap), to calculate the relative risk for a subpopulation, RR=Bp/Ap. We estimated RR for several age groups using data on reported influenza A cases in Germany between 2002-2017.

Results

Children aged 14-17y had the highest RR estimates for 7 out of 15 influenza A epidemics in the data, including the 2009 pandemic, and the large 2016/17, 2008/09, and 2006/07 seasons. Children aged 10-13y had the highest RR estimates during 3 epidemics, including the large 2014/15 and 2004/05 seasons. Children aged 6-9y had the highest RR estimates during two epidemics, including the large 2012/13 season. Children aged 2-5y had the highest RR estimate during the moderate 2015/16 season; adults aged 18-24y had the highest RR estimate during the small 2005/06 season; adults aged 25-34y had the highest RR estimate during the large, 2002/03 season.

Conclusions

Our results support the prominent role of all school-age children, particularly the oldest ones, in propagating influenza epidemics in the community. We note that national vaccination coverage levels among older school-age children were lower than among younger school-age children during the recent influenza seasons in the US, and influenza vaccination program in England has not been phased in yet for secondary school students.
RecoverY: K-mer based read classification for Y-chromosome specific sequencing and assembly
Authors: Rangavittal Samarth , Harris Robert S. , Cechova Monika , Tomaszkiewicz Marta , Chikhi Rayan , Makova Kateryna D. , Medvedev Paul
Published: June 2017

Motivation

The haploid mammalian Y chromosome is usually under-represented in genome assemblies due to high repeat content and low depth due to its haploid nature. One strategy to ameliorate the low coverage of Y sequences is to experimentally enrich Y-specific material before assembly. Since the enrichment process is imperfect, algorithms are needed to identify putative Y-specific reads prior to downstream assembly. A strategy that usesk-mer abundances to identify such reads was used to assemble the gorilla Y (Tomaszkiewicz et al 2016). However, the strategy required the manual setting of key parameters, a time-consuming process leading to sub-optimal assemblies.

Results

We develop a method, RecoverY, that selects Y-specific reads by automatically choosing the abundance level at which a k-mer is deemed to originate from the Y. This algorithm uses prior knowledge about the Y chromosome of a related species or known Y transcript sequences. We evaluate RecoverY on both simulated and real data, for human and gorilla, and investigate its robustness to important parameters. We show that RecoverY leads to a vastly superior assembly compared to alternate strategies of filtering the reads or contigs. Compared to the preliminary strategy used in Tomaszkiewicz et al (2016), we achieve a 33% improvement in assembly size and a 20% improvement in the NG50, demonstrating the power of automatic parameter selection.

Availability

Our tool RecoverY is freely available athttps://github.com/makovalab-psu/RecoverY

Contact

kmakova@bx.psu.edu,pashadag@cse.psu.edu

Supplementary information

Attached as an additional file.
Reduced chlorhexidine and daptomycin susceptibility arises in vancomycin-resistantEnterococcus faeciumafter serial chlorhexidine exposure
Authors: Bhardwaj Pooja , Hans Amrita , Ruikar Kinnari , Guan Ziqiang , Palmer Kelli L.
Published: June 2017

Vancomycin-resistantEnterococcus faecium(VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a bisbiguanide cationic antiseptic that is routinely used for patient bathing and other infection control practices. VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX exposure have not been studied in enterococci. In this study, we serially exposed VREfm to increasing concentrations of CHX for a period of 21 days in two independent experimental evolution trials. Reduced CHX susceptibility emerged (4-fold shift in CHX MIC). Sub-populations with reduced daptomycin (DAP) susceptibility were detected, which were further analyzed by genome sequencing and lipidomic analysis. Across the trials, we identified adaptive changes in genes with predicted or experimentally confirmed roles in chlorhexidine susceptibility (efrE), global nutritional stress response (relA), nucleotide metabolism (cmk), phosphate acquisition (phoU), and glycolipid biosynthesis (bgsB), among others. Moreover, significant alterations in membrane phospholipids were identified. Our results are clinically significant because they identify a link between serial sub-inhibitory CHX exposure and reduced DAP susceptibility. In addition, the CHX-induced genetic and lipidomic changes described in this study offer new insights into the mechanisms underlying the emergence of antibiotic resistance in VREfm.
Dark Control: Towards a Unified Account of Default Mode Function by Markov Decision Processes
Authors: Dohmatob Elvis , Dumas Guillaume , Bzdok Danilo
Published: June 2017

The default mode network (DMN) is believed to subserve the baseline mental activity in humans. Its highest energy consumption compared to other brain networks and its intimate coupling with conscious awareness are both pointing to an overarching function. Many research streams speak in favor of an evolutionarily adaptive role in envisioning experience to anticipate the future. In the present work, we propose aprocess modelthat tries to explainhowthe DMN may implement continuous evaluation and prediction of the environment to guide behavior. Specifically, we answer the question whether the neurobiological properties of the DMN collectively provide the computational building blocks necessary for a Markov Decision Process. We argue that our formal account of DMN function naturally accommodates as special cases previous interpretations based on (1) predictive coding, (2) semantic associations, and (3) a sentinel role. Moreover, this process model for the neural optimization of complex behavior in the DMN offers parsimonious explanations for recent experimental findings in animals and humans.
Replicating and cycling stores of information perpetuate life
Authors: Jose Antony M.
Published: June 2017

Life is perpetuated through a single-cell bottleneck between generations in many organisms. Here, I highlight that this cell holds information in two distinct forms: in the linear DNA sequence that is replicated during cell divisions, and in the three-dimensional arrangement of molecules that can change during development but that is recreated at the start of each generation. These two interdependent stores of information – one replicating with each cell division and the other cycling with a period of one generation – coevolve while perpetuating an organism. Unlike the genome, the cycling arrangement of molecules, which could include RNAs, proteins, sugars, lipids, etc., is not well understood. Because this arrangement and the genome are together transmitted from one generation to the next, analysis of both is necessary to understand evolution, origins of inherited diseases, and consequences of genome engineering. Recent developments suggest that tools are in place to examine how all the information to build an organism is encoded within a single cell, and how this cell code is reproduced in every generation.
Research Synergy and Drug Development: Bright Stars in Neighboring Constellations
Authors: Keserci Samet , Livingston Eric B. , Wan Lingtian , Pico Alexander R. , Chacko George
Published: June 2017

Drug discovery and subsequent availability of a new breakthrough therapeutic or ‘cure’ is a compelling example of societal benefit from research advances. These advances are invariably collaborative, involving the contributions of many scientists to a discovery network in which theory and experiment are built upon. To understand such scientific advances, data mining of public and commercial data sources coupled with network analysis can be used as a digital methodology to assemble and analyze component events in the history of a therapeutic. This methodology is extensible beyond the history of therapeutics and its use more generally supports (i) efficiency in exploring the scientific history of a research advance (ii) documenting and understanding collaboration (iii) portfolio analysis, planning and optimization (iv) communication of the societal value of research. As a proof of principle, we have conducted a case study of five anti-cancer therapeutics. We have linked the work of roughly 237,000 authors in 106,000 scientific publications that capture the research crucial for the development of these five therapeutics. We have enriched the content of networks of these therapeutics by annotating them with information on research awards as well as peer review that preceded these awards. Applying retrospective citation discovery, we have identified a core set of publications cited in the networks of all five therapeutics and additional intersections in combinations of networks as well as awards from the National Institutes of Health that supported this research. Lastly, we have mapped these awards to their cognate peer review panels, identifying another layer of collaborative scientific activity that influenced the research represented in these networks.
Approximate inference of gene regulatory network models from RNA-Seq time series data
Authors: Thorne Thomas
Published: June 2017

Inference of gene regulatory network structures from RNA-Seq data is challenging due to the nature of the data, as measurements take the form of counts of reads mapped to a given gene. Here we present a model for RNA-Seq time series data that applies a negative binomial distribution for the observations, and uses sparse regression with a horseshoe prior to learn a dynamic Bayesian network of interactions between genes. We use a variational inference scheme to learn approximate posterior distributions for the model parameters. The methodology is benchmarked on synthetic data designed to replicate the distribution of real world RNA-Seq data. We compare our method to other sparse regression approaches and information theoretic methods. We demonstrate an application of our method to a publicly available human neuronal stem cell differentiation RNA-Seq time series.
Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly
Authors: Aneichyk Tatsiana , Hendriks William.T. , Yadav Rachita , Shin David , Gao Dadi , Vaine Christine A. , Collins Ryan L. , Stortchevoi Alexei , Currall Benjamin , Brand Harrison , Hanscom Carrie , Antolik Caroline , Dy Marisela , Ragavendran Ashok , Acuña Patrick , Go Criscely , Sapir Yechiam , Wainger Brian J. , Henderson Daniel , Dhakal Jyotsna , Ito Naoto , Weisenfeld Neil , Jaffe David , Sharma Nutan , Breakefield Xandra O. , Ozelius Laurie J. , Bragg D. Cristopher , Talkowski Michael E.
Published: June 2017

X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease endemic to the Philippines. We integrated genome and transcriptome assembly with induced pluripotent stem cell-based modeling to identify the XDP causal locus and potential pathogenic mechanism. Genome sequencing identified novel variation that was shared by all probands and three recombination events that narrowed the causal locus to a genomic segment includingTAF1. Transcriptome assembly in neural derivative cells discovered novelTAF1transcripts, including a truncated transcript exclusively observed in probands that involved aberrant splicing and intron retention (IR) associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion. This IR correlated with decreased expression of the predominantTAF1transcript and altered expression of neurodevelopmental genes; both the IR and aberrantTAF1expression patterns were rescued by CRISPR/Cas9 excision of the SVA. These data suggest a unique genomic cause of XDP and may provide a roadmap for integrative genomic studies in other unsolved Mendelian disorders.

Highlights

Genome assembly narrows the XDP causal locus to a segment includingTAF1

XDP-specific SVA insertion induces intron retention and down-regulation ofTAF1

CRISPR/Cas9 excision of SVA rescues aberrant splicing and cTAF1 expression in XDP

Gene networks perturbed in proband cells associate to synapse and neurodevelopment
Sparse coding and dimensionality reduction in cortex
Authors: Beyeler Michael , Rounds Emily , Carlson Kristofor D. , Dutt Nikil , Krichmar Jeffrey L.
Published: June 2017

Supported by recent computational studies, sparse coding and dimensionality reduction are emerging as a ubiquitous coding strategy across brain regions and modalities, allowing neurons to achieve nonnegative sparse coding (NSC) by efficiently encoding high-dimensional stimulus spaces using a sparse and parts-based population code. Reducing the dimensionality of complex, multimodal sensory streams is critically important for metabolically constrained brain areas to represent the world. In this article, we provide an overview of NSC, summarize evidence for its role in neural computation in disparate regions of the brain, ranging from visual processing to spatial navigation, and speculate that specific forms of synaptic plasticity and homeostatic modulation may underlie its implementation. We suggest that NSC may be an organizing principle in the nervous system.
An extinct hummingbird species that never was: a cautionary tale about sampling issues in molecular phylogenetics
Authors: Pérez-Emán Jorge L. , Perdigón Ferreira Jhoniel , Gutiérrez-Pinto Natalia , Cuervo Andrés M. , Céspedes Laura N. , Witt Christopher C. , Cadena Carlos Daniel
Published: June 2017

The Bogota Sunangel (Heliangelus zusii) was described based on a historical specimen lacking locality data as a striking–and potentially extinct– new species of hummingbird more than two decades ago. However, it was considered a dubious taxon by some researchers until a molecular study with strong species-level taxon sampling revealed its phylogenetic affinities and validated its status as a distinct species. We reanalysed existing mitochondrial DNA data together with a new data set sampling multiple populations of the Long-tailed Sylph (Aglaiocercus kingii), a species broadly distributed in the Andes of South America. In contrast to previous work, we found thatH. zusiishares a haplotype with specimens ofA. kingiifrom the Eastern Cordillera of Colombia, which is phylogenetically nested within a clade formed by populations ofA. kingiifrom the Colombian Andes. These results suggest thatH. zusiiis not a distinct species, but is most likely the result of hybridization between a femaleA. kingiiand a male of another hummingbird species. These findings highlight the importance of thorough taxonomic and geographic sampling when assessing the likelihood of hybrid origin of an organism, particularly in cases potentially involving wide-ranging species in areas where deep phylogeographic structure is likely.
Pericyte ontogeny: the use of chimeras to track a cell lineage of diverse germ line origins
Authors: Etchevers Heather C.
Published: June 2017

The goal of lineage tracing is to understand body formation over time by discovering which cells are the progeny of a specific, identified, ancestral progenitor. Subsidiary questions include unequivocal identification of what they have become, how many descendants develop, whether they live or die, and where they are located in the tissue or body at the end of the window examined. A classical approach in experimental embryology, lineage tracing continues to be used in developmental biology, stem cell and cancer research, wherever cellular potential and behavior need to be studied in multiple dimensions, of which one is time. Each technical approach has its advantages and drawbacks. This chapter, with some previously unpublished data, will concentrate non-exclusively on the use of interspecies chimeras to explore the origins of perivascular (or mural) cells, of which those adjacent to the vascular endothelium are termed pericytes for this purpose. These studies laid the groundwork for our understanding that pericytes derive from progenitor mesenchymal pools of multiple origins in the vertebrate embryo, some of which persist into adulthood. The results obtained through xenografting, like in the methodology described here, complement those obtained through genetic lineage tracing techniques within a given species.
High contiguityArabidopsis thalianagenome assembly with a single nanopore flow cell
Authors: Michael Todd P. , Jupe Florian , Bemm Felix , Timothy Motley S. , Sandoval Justin P. , Loudet Olivier , Weigel Detlef , Ecker Joseph R.
Published: June 2017

While many evolutionary questions can be answered by short read re-sequencing, presence/absence polymorphisms of genes and/or transposons have been largely ignored in large-scale intraspecific evolutionary studies. To enable the rigorous analysis of such variants, multiple high quality and contiguous genome assemblies are essential. Similarly, while genome assemblies based on short reads have made genomics accessible for non-reference species, these assemblies have limitations due to low contiguity. Long-read sequencers and long-read technologies have ushered in a new era of genome sequencing where the lengths of reads exceed those of most repeats. However, because these technologies are not only costly, but also time and compute intensive, it has been unclear how scalable they are. Here we demonstrate a fast and cost effective reference assembly for anArabidopsis thalianaaccession using the USB-sized Oxford Nanopore MinION sequencer and typical consumer computing hardware (4 Cores, 16Gb RAM). We assemble the accession KBS-Mac-74 into 62 contigs with an N50 length of 12.3 Mb covering 100% (119 Mb) of the non-repetitive genome. We demonstrate that the polished KBS-Mac-74 assembly is highly contiguous with BioNano optical genome maps, and of high per-base quality against a likewise polished Pacific Biosciences long-read assembly. The approach we implemented took a total of four days at a cost of less than 1,000 USD for sequencing consumables including instrument depreciation.
EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment
Authors: Eva Richard , Koseki Hiroaki , Kanamarlapudi Venkateswarlu , Fawcett James W.
Published: June 2017

It is not clear why central nervous system (CNS) axons lose their intrinsic ability to regenerate with maturity, whilst peripheral (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their rab11 positive carriers. We reasoned that this exclusion might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this hypothesis using laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 GEF EFA6. EFA6 exerts its effects from a previously unreported location within the axon initial segment (AIS). EFA6 does not localise here in DRG axons, and in these neurons, ARF activation is counteracted by an ARF-GAP which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whilst overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the axon initial segment, signalling and transport.

Summary Statement

We identify a novel resident of the axon initial segment, EFA6. This functions to prevent growth-promoting molecules from entering mature CNS axons. Removing EFA6 elevates the axon’s regenerative potential.