bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets
Authors: Wang Ling , Conner James M. , Nagahara Alan H. , Tuszynski Mark H.
Published: February 2016

Significance

Rehabilitation is often prescribed after brain injury, but the basis for how training can influence brain plasticity and recovery is unclear. In this study, we show that intense rehabilitation training after focal brain injury drives significant structural changes in brain cells located adjacent to the injury. Importantly, a key brain modulatory system, the basal forebrain cholinergic system, is required for enabling rehabilitation to impact brain structure. Damage to the cholinergic system, which can occur naturally during aging, completely blocks brain plasticity mediated by rehabilitation and significantly attenuates functional recovery. These results provide new insights into how rehabilitation may promote recovery and suggest that brain cholinergic systems may be a possible therapeutic target for influencing recovery.
Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates
Authors: Peng Chen , Haller Sherry L. , Rahman Masmudur M. , McFadden Grant , Rothenburg Stefan
Published: February 2016

Significance

The virulence and host range of viruses is controlled by the interaction of the host innate immune system with viral molecules. This interaction is an important driver for the evolution of both the host and the virus. The attenuation of myxoma virus, a rabbit-specific poxvirus, after its deliberate release to control European rabbit populations, and the increased resistance of the rabbits, is one of the best-known examples for host–virus coevolution on the population level. We show that the myxoma virus protein M156 specifically inhibited the antiviral protein kinase R (PKR) from rabbits but not PKR from other mammals, that PKR inhibition correlated with virus replication during infection, and that M156 contains a loss-of-function mutation in Australian field isolates.
Antarctic ice sheet sensitivity to atmospheric CO
2
variations in the early to mid-Miocene
Authors: Levy Richard , Harwood David , Florindo Fabio , Sangiorgi Francesca , Tripati Robert , von Eynatten Hilmar , Gasson Edward , Kuhn Gerhard , Tripati Aradhna , DeConto Robert , Fielding Christopher , Field Brad , Golledge Nicholas , McKay Robert , Naish Timothy , Olney Matthew , Pollard David , Schouten Stefan , Talarico Franco , Warny Sophie , Willmott Veronica , Acton Gary , Panter Kurt , Paulsen Timothy , Taviani Marco ,   SMS Science Team, Acton Gary , Askin Rosemary , Atkins Clifford , Bassett Kari , Beu Alan , Blackstone Brian , Browne Gregory , Ceregato Alessandro , Cody Rosemary , Cornamusini Gianluca , Corrado Sveva , DeConto Robert , Del Carlo Paola , Di Vincenzo Gianfranco , Dunbar Gavin , Falk Candice , Field Brad , Fielding Christopher , Florindo Fabio , Frank Tracy , Giorgetti Giovanna , Grelle Thomas , Gui Zi , Handwerger David , Hannah Michael , Harwood David M , Hauptvogel Dan , Hayden Travis , Henrys Stuart , Hoffmann Stefan , Iacoviello Francesco , Ishman Scott , Jarrard Richard , Johnson Katherine , Jovane Luigi , Judge Shelley , Kominz Michelle , Konfirst Matthew , Krissek Lawrence , Kuhn Gerhard , Lacy Laura , Levy Richard , Maffioli Paola , Magens Diana , Marcano Maria C. , Millan Cristina , Mohr Barbara , Montone Paola , Mukasa Samuel , Naish Timothy , Niessen Frank , Ohneiser Christian , Olney Mathew , Panter Kurt , Passchier Sandra , Patterson Molly , Paulsen Timothy , Pekar Stephen , Pierdominici Simona , Pollard David , Raine Ian , Reed Joshua , Reichelt Lucia , Riesselman Christina , Rocchi Sergio , Sagnotti Leonardo , Sandroni Sonia , Sangiorgi Francesca , Schmitt Douglas , Speece Marvin , Storey Bryan , Strada Eleonora , Talarico Franco , Taviani Marco , Tuzzi Eva , Verosub Kenneth , von Eynatten Hilmar , Warny Sophie , Wilson Gary , Wilson Terry , Wonik Thomas , Zattin Massimiliano
Published: February 2016

Significance

New information from the ANDRILL-2A drill core and a complementary ice sheet modeling study show that polar climate and Antarctic ice sheet (AIS) margins were highly dynamic during the early to mid-Miocene. Changes in extent of the AIS inferred by these studies suggest that high southern latitudes were sensitive to relatively small changes in atmospheric CO
2
(between 280 and 500 ppm). Importantly, reconstructions through intervals of peak warmth indicate that the AIS retreated beyond its terrestrial margin under atmospheric CO
2
conditions that were similar to those projected for the coming centuries.
Cortical cholinergic signaling controls the detection of cues
Authors: Gritton Howard J. , Howe William M. , Mallory Caitlin S. , Hetrick Vaughn L. , Berke Joshua D. , Sarter Martin
Published: February 2016

Significance

Virtually the entire cortex is innervated by cholinergic projections from the basal forebrain. Traditionally, this neuronal system has been described as a neuromodulator system that supports global states such as cortical arousal. The presence of fast and regionally specific bursts in cholinergic neurotransmission suggests a more specialized role in cortical processing. Here we used optogenetic methods to investigate the capacity of phasic cholinergic signaling to control behavior. Our findings indicate a causal role of phasic cholinergic signaling in using external cues to guide behavioral choice. These findings indicate the significance of phasic cholinergic activity and also illustrate the potential impact of abnormal, phasic cholinergic neurotransmission on fundamental cognitive functions that involve cue-based behavioral decisions.
Social wasps are a
Saccharomyces
mating nest
Authors: Stefanini Irene , Dapporto Leonardo , Berná Luisa , Polsinelli Mario , Turillazzi Stefano , Cavalieri Duccio
Published: February 2016

Significance

Despite the widespread interest on
Saccharomyces cerevisiae
, its wild lifestyle is far from being completely understood, with one of the most resounding examples being its sexual attitude. We show that the intestine of social wasps favors the mating of
Saccharomyces
strains by providing a succession of environmental conditions prompting sporulation and germination. We also demonstrate that the insect intestine favors hybridization of
S. cerevisiae
and
Saccharomyces paradoxus
. Although
S. paradoxus
survives in wild environments and rarely mates with
S. cerevisiae
, we discover that two European
S. paradoxus
strains cannot survive the wasp's intestinal environment but can be rescued through interspecific hybridization with
S. cerevisiae
. These findings are introducing insects as environmental alcoves in which yeast cells can meet and mate.
Temperature-driven global sea-level variability in the Common Era
Authors: Kopp Robert E. , Kemp Andrew C. , Bittermann Klaus , Horton Benjamin P. , Donnelly Jeffrey P. , Gehrels W. Roland , Hay Carling C. , Mitrovica Jerry X. , Morrow Eric D. , Rahmstorf Stefan
Published: February 2016

Significance

We present the first, to our knowledge, estimate of global sea-level (GSL) change over the last ∼3,000 years that is based upon statistical synthesis of a global database of regional sea-level reconstructions. GSL varied by ∼±8 cm over the pre-Industrial Common Era, with a notable decline over 1000–1400 CE coinciding with ∼0.2 °C of global cooling. The 20th century rise was extremely likely faster than during any of the 27 previous centuries. Semiempirical modeling indicates that, without global warming, GSL in the 20th century very likely would have risen by between −3 cm and +7 cm, rather than the ∼14 cm observed. Semiempirical 21st century projections largely reconcile differences between Intergovernmental Panel on Climate Change projections and semiempirical models.
Contraction of the type I IFN locus and unusual constitutive expression ofIFN-αin bats
Authors: Zhou Peng , Tachedjian Mary , Wynne James W. , Boyd Victoria , Cui Jie , Smith Ina , Cowled Christopher , Ng Justin H. J. , Mok Lawrence , Michalski Wojtek P. , Mendenhall Ian H. , Tachedjian Gilda , Wang Lin-Fa , Baker Michelle L.
Published: February 2016

Significance

Here we provide what is, to our knowledge, the first gene map of the type I IFN region of any bat species with the sequence of the type I IFN locus of the Australian black flying fox,Pteropus alecto.The bat IFN locus contains fewer IFN genes compared with any other mammal sequenced to date, including only threeIFN-αgenes. We also demonstrate that batIFN-αgenes are constitutively expressed in unstimulated bat tissues and cells and that their expression is unaffected by viral infection. This unusual pattern ofIFN-αexpression has not been described in any other species to our knowledge and has important implications for the role of innate immunity in the ability of bats to coexist with viruses in the absence of disease.
Brown adipose tissue transplantation ameliorates polycystic ovary syndrome
Authors: Yuan Xiaoxue , Hu Tao , Zhao Han , Huang Yuanyuan , Ye Rongcai , Lin Jun , Zhang Chuanhai , Zhang Hanlin , Wei Gang , Zhou Huiqiao , Dong Meng , Zhao Jun , Wang Haibin , Liu Qingsong , Lee Hyuek Jong , Jin Wanzhu , Chen Zi-Jiang
Published: February 2016

Significance

In the current study, we show that brown adipose tissue (BAT) activity is dramatically reduced in a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) rat when compared with a normal control rat. Importantly, the key features of PCOS (such as insulin resistance and irregular estrous cycle) are alleviated after BAT transplantation. Mechanistically, transplanted BAT enhances endogenous BAT activity and thereby increases the circulating adiponectin level, which was lower in both the PCOS patient and PCOS rat model. Furthermore, exogenous adiponectin protein administration recapitulates beneficial effects from BAT transplantation in a PCOS rat. Taken together, these data highlight the important role of BAT in the development of PCOS and that BAT-induced adiponectin might open up a new way in the treatment of PCOS.
Identification and quantitation of lipid C=C location isomers: A shotgun lipidomics approach enabled by photochemical reaction
Authors: Ma Xiaoxiao , Chong Leelyn , Tian Ran , Shi Riyi , Hu Tony Y. , Ouyang Zheng , Xia Yu
Published: February 2016

Significance

Unsaturated lipids constitute a significant portion of total lipids in mammalian cells. They fulfill different biological roles and often exist in isomeric structures that differ only in the locations of carbon-carbon double (C=C) bonds. A long-standing challenge in lipidomics is the identification and quantitation of lipid C=C location isomers at adequate sensitivity. In this study, we have developed a solution to this challenge by implementing online photochemical derivatization (Paternò–Büchi reaction) with tandem mass spectrometry into a shotgun lipidomics workflow. The method is widely applicable for different classes of lipids and is sensitive, fast, and compatible with different MS platforms. It shall serve as an enabling tool for advancing studies in lipid biology and biomarker discovery.
A
PERIOD3
variant causes a circadian phenotype and is associated with a seasonal mood trait
Authors: Zhang Luoying , Hirano Arisa , Hsu Pei-Ken , Jones Christopher R. , Sakai Noriaki , Okuro Masashi , McMahon Thomas , Yamazaki Maya , Xu Ying , Saigoh Noriko , Saigoh Kazumasa , Lin Shu-Ting , Kaasik Krista , Nishino Seiji , Ptáček Louis J. , Fu Ying-Hui
Published: February 2016

Significance

It has long been thought that sleep and mood are intimately connected in humans, but at present there are no known molecular links. We identified rare variants in the
PERIOD3
gene in persons with both altered sleep behavior and features of seasonal affective disorder. We show that these variants recapitulate circadian and mood phenotypes in mouse models. Although we were not able to test mood in fruit flies, we did uncover a sleep trait similar to that seen in humans in flies carrying the human variants. Our molecular studies reveal that the variants led to less stable PER3 protein and reduced the stabilizing effect of PER3 on PER1/PER2, providing a mechanistic explanation for the circadian trait.
Contrasting responses within a single neuron class enable sex-specific attraction in
Caenorhabditis elegans
Authors: Narayan Anusha , Venkatachalam Vivek , Durak Omer , Reilly Douglas K. , Bose Neelanjan , Schroeder Frank C. , Samuel Aravinthan D. T. , Srinivasan Jagan , Sternberg Paul W.
Published: February 2016

Significance

Roundworms carry out crucial sensory behaviors with a relatively small number of neurons. We find that male roundworms have strong preferences for particular concentrations of sex-specific small molecule cues secreted by their potential mates. These preferences emerge from the dynamics of a population of four apparently identical male-specific neurons. The response of these sensory neurons is not uniform, with some being excitatory and others inhibitory, and the timing of response varies with concentration. These features allow this single neuronal class to prefer a concentration, and potentially to calculate a derivative of chemical concentration. This previously uncharacterized neural coding strategy might allow nematodes to efficiently use a small number of cells to carry out a crucial computation to enact innate social behaviors.
Axin2
marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/β-catenin signaling
Authors: Lim Xinhong , Tan Si Hui , Yu Ka Lou , Lim Sophia Beng Hui , Nusse Roeland
Published: February 2016

Significance

Hair follicle stem cells (HFSCs) remain quiescent for long periods of time during the resting phase of the hair cycle. How they maintain their stemness and identity during quiescence while being responsive to growth-inducing cues remains poorly understood. Here, we identify
Axin2
as a previously unidentified marker of HFSCs and use it to show that quiescent HFSCs undergo and require active Wnt/β-catenin signaling. By mapping Wnt and its inhibitors with high sensitivity, we show that HFSCs secrete their own self-renewing Wnt signals and inhibitors that promote differentiation outside of the stem cell compartment. Our findings suggest that careful modulation of Wnt signaling may be important for the derivation and maintenance of HFSCs for alopecia treatment and drug screens.
Organizing the Production of Variscite Personal Ornaments in Later Prehistoric Iberia: The Mines of Aliste and the Production Sites of Quiruelas de Vidriales (Zamora, Spain)
Authors: García Rodrigo Villalobos , Odriozola Carlos P.
Published: February 2016

Green objects of personal adornment were quite common among Neolithic and Copper Age groups in Western Europe, and variscite was one of the minerals that was most often used for such a purpose. This article presents the results of a series of archaeological campaigns designed to study the mines of Aliste and the ornament production loci of Quiruelas de Vidriales (both in the province of Zamora, Spain). We discovered that initially, during the fourth millennium cal BC, variscite from Aliste was seldom used and the ornaments’ production was dispersed, but that there was a significant shift during the third millennium cal BC: ornament production intensified and became concentrated in the production sites of Quiruelas. We relate this transformation to the socioeconomic processes that developed in the Iberian Peninsula and the growth of supra-regional socio-technical artefact exchange networks.
Higher bone mass in prepubertal and peripubertal female footballers
Authors: Plaza‐Carmona M. , Vicente‐Rodríguez G. , Gómez‐Cabello A. , Martín‐García M. , Sánchez‐Sánchez J. , Gallardo L. , Ara I.
Published: February 2016

Objectives: The main aim of this study was to compare the bone mass of female football players with controls of different pubertal stages. Methods: Sixty five girls aged 8–14 years (10.14 ± 0.1, Tanner stages I–IV) participated in the study. Twenty participants were prepubertal (10 prepubertal control) and 45 peripubertal (15 peripubertal control). All footballers trained two days per week while the control group did not perform regular physical activity outside of school. Body composition was assessed by Dual‐energy X‐ray absorptiometry. Analysis of covariance was performed to evaluate differences in lean and bone masses. Results: Significant differences in lower‐body extremities lean mass (LLM) between peripubertal groups were found (P < .05). Additionally, prepubertal footballers showed higher values of bone mineral content (BMC) at the femoral neck (P < .05) while peripubertal footballers exhibited enhanced BMC at the whole‐body, trochanter and Wards triangle area. Bone mineral density (BMD) was higher in footballers compared to their non‐active peers at the femoral neck and intertrochanter (P < .05, respectively) while in the peripubertal footballers higher BMD values were found in almost all of the studied body sites. Conclusion: Female footballers showed higher bone and lean masses compared to control counterparts; these differences are already detectable at prepubertal ages and more consistent after pubertal spurt.
The self that remains: a symbolic analysis of the psychological death of the self in Alzheimer's disease
Authors: Blandin Kesstan
Published: February 2016

In Alzheimer's disease, we witness a psychologicaldeath of the selfbefore physical death. The unraveling of the self that occurs in Alzheimer's disease is a classic underworld journey, through which the deceased undergo a dismantling of memory and temporal identity to become shades of the Underworld. Through stories of family members living with dementia in a loved one, Alzheimer's disease reveals a descent into an irrational, symbolic, and timeless otherworld. This unique dying process provides insight into a degeneration and death of self and identity that is always occurring in the undergrowth of individuation. Individuation, as explicated through Greek eschatology, has two aspects: a general, phylogeneticHomericprocess, and an ontogeneticOrphicprocess characterized by intentional participation in one's own evolution of consciousness. Analyses of an archetypal death, a symbolic birth, and the self that remains as temporal identity is deconstructed through dementia conclude the article.
NBR1 enables autophagy-dependent focal adhesion turnover
Authors: Kenific Candia M. , Stehbens Samantha J. , Goldsmith Juliet , Leidal Andrew M. , Faure Nathalie , Ye Jordan , Wittmann Torsten , Debnath Jayanta
Published: February 2016

Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells.
Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation
Authors: Squarr Anna Julia , Brinkmann Klaus , Chen Baoyu , Steinbacher Tim , Ebnet Klaus , Rosen Michael K. , Bogdan Sven
Published: February 2016

Directional cell movements during morphogenesis require the coordinated interplay between membrane receptors and the actin cytoskeleton. The WAVE regulatory complex (WRC) is a conserved actin regulator. Here, we found that the atypical cadherin Fat2 recruits the WRC to basal membranes of tricellular contacts where a new type of planar-polarized whip-like actin protrusion is formed. Loss of either Fat2 function or its interaction with the WRC disrupts tricellular protrusions and results in the formation of nonpolarized filopodia. We provide further evidence for a molecular network in which the receptor tyrosine phosphatase Dlar interacts with the WRC to couple the extracellular matrix, the membrane, and the actin cytoskeleton during egg elongation. Our data uncover a mechanism by which polarity information can be transduced from a membrane receptor to a key actin regulator to control collective follicle cell migration during egg elongation. 4D-live imaging of rotating MCF10A mammary acini further suggests an evolutionary conserved mechanism driving rotational motions in epithelial morphogenesis.
Rotating for elongation: Fat2 whips for the race
Authors: Stürner Tomke , Tavosanis Gaia
Published: February 2016

Dynamic rearrangements of the actin cytoskeleton are crucial for cell shape and migration. In this issue, Squarr et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508081) show that the cadherin superfamily protein Fat2 regulates actin-rich protrusions driving collective cell migration during Drosophila melanogaster egg morphogenesis through its interaction with the WAVE regulatory complex.
Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
Authors: Hu Hongbo , Wang Hui , Xiao Yichuan , Jin Jin , Chang Jae-Hoon , Zou Qiang , Xie Xiaoping , Cheng Xuhong , Sun Shao-Cong
Published: February 2016

Signal transduction from the T cell receptor (TCR) is crucial for T cell–mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell–mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function.
Range expansion of invasive shrubs: implication for crown fire risk in forestlands of the southern USA
Authors: Wang Hsiao-Hsuan , Wonkka Carissa L. , Grant William E. , Rogers William E.
Published: February 2016

Non-native plant invasions and changing management activities have dramatically altered the structure and composition of forests worldwide. Invasive shrubs and fire suppression have led to increased densification and biomass accumulation in forest ecosystems of the southeastern USA. Notably, Chinese and European privets are rapid growing, shade-tolerant shrubs which number among the most aggressive invasive species in these forests. Privet encroachment has caused losses of native diversity, alteration of ecosystem processes and changes in community structure. The latter has become manifest through decreases in fine herbaceous fuels concurrent with increases in coarse woody fuels in forest understoreys. These alterations in fuel structure will potentially lead to less frequent, but more severe forest fires, which threaten important forest resources during extreme weather conditions. Drawing on extensive data sets compiled by the US Forest Service, we integrated statistical forecasting and analytical techniques within a spatially explicit, agent-based, simulation framework to predict potential range expansion of Chinese and European privet ( Ligustrum sinense and L. vulgare ) and the associated increase in crown fire risk over the next two decades in forestlands of Mississippi and Alabama. Our results indicate that probability of invasion is positively associated with elevation, adjacency (within 300 m) to water bodies, mean daily maximum temperature, site productivity and private land ownership, and is negatively associated with slope, stand age, artificial regeneration, distance to the nearest road and fire disturbance. Our projections suggest the total area invaded will increase from 1.36 to ≈31.39% of all forestlands in Mississippi and Alabama (≈7 million hectares) and the annual frequency of crown fires in these forestlands will approximately double within the next two decades. Such time series projections of annual range expansions and crown fire frequency should provide land managers and restoration practitioners with an invasion chronology upon which to base proactive management plans.
Modified Mini-open Transforaminal Lumbar Interbody Fusion
Authors: Pakzaban Peyman
Published: February 2016

Study Design.

Retrospective case series.

Objective.

To describe a modified technique for mini-open transforaminal lumbar interbody fusion (TLIF) that improves visualization for decompression, fusion, and freehand pedicle screw insertion. Accuracy of freehand pedicle screw placement with this technique was assessed.

Summary of Background Data.

Mini-open TLIF is a minimally invasive technique that allows limited visualization of the bone and neural anatomy via an expandable tubular retractor inserted through the Wiltse plane. No significant modification that of this technique has been described in detail.

Methods.

In this study, 92 consecutive patients underwent one-level modified mini-open TLIF (MOTLIF). MOTLIF modifications consisted of (i) transmuscular dissection through the multifidus muscle rather than intermuscular dissection in the Wiltse plane; (ii) microsurgical detachment of multifidus from the facet rather than muscle dilation; (iii) en bloc total facetectomy (unilateral or bilateral, as needed for decompression); (iv) facet autograft used for interbody fusion; and (v) solid pedicle screws placed bilaterally by a freehand technique under direct vision.

Results.

The mean age was 53 years. Mean follow-up was 35 months (minimum 2 yrs). By 6 months, mean Visual Analog Scale for back and leg pain had improved from 51 to 19 and from 58 to 17, respectively, and mean Oswestry Disability Index (ODI) improved from 53 to 16. These improvements persisted at 2 years. Solid fusion, defined by computed tomography at 1 year, was achieved in 88.1%, whereas satisfactory fusion was achieved in 95.2% of patients. Pedicle screws were accurately placed in 335 of 336 imaged pedicles (pedicle breach grades: 91.1% grade 1; 8.6% grade 2; and 0.3% grade 3). Mean fluoroscopy time was 29.3 seconds.

Conclusion.

MOTLIF is a safe and effective minimally invasive technique with a high fusion rate. It allows accurate pedicle screw placement by a freehand technique. By eliminating bi-planar fluoroscopy, it helps reduce radiation exposure. This is the largest published report of mini-open TLIF to date.

Level of Evidence: 4
Single-stage Treatment of Osteomyelitis of the Cervical Spine Using Anterior Instrumentation and Titanium Mesh Cages
Authors: Zhang Zhen-xing , Li Tao , Hao Ding-jun
Published: February 2016

Study Design.

A case series.

Objective.

The aim of this study was to evaluate the clinical outcomes of patients with osteomyelitis of the cervical spine who were treated with single-stage anterior debridement and fusion using titanium mesh cages along with anterior plates.

Summary of Background Data.

There have been few studies in single-stage surgical treatment of osteomyelitis of the cervical spine using titanium mesh cages along with anterior plates.

Methods.

Twenty-four patients treated for osteomyelitis of the cervical spine are presented. There were 11 male and 13 female with an average age of 53.3 years (42–63). Seventeen patients presented with a neurologic deficit at the time of diagnosis. Surgical treatment consisted of anterior debridement and fusion using titanium mesh cages along with anterior plates as a one-step procedure. The patients’ records and radiographs were retrospectively analyzed and follow-up clinical and radiographic data obtained.

Results.

The median follow-up period was 52 months. There were no implant failures. All patients showed a solid bony fusion without any recurrence of infection at latest follow-up. Changes in pain level, hematologic parameters, and neurologic status demonstrated a significant clinical improvement in all patients.

Conclusion.

This single-stage surgical treatment for osteomyelitis of the cervical spine provided satisfactory results. There is no increased risk of recurrence or persistence of infection related to the implantation of titanium mesh cages and instrumentation.

Level of Evidence: 4
Extending Colorectal Cancer Screening to Persons Aged 40 to 49 Years With Immunochemical Fecal Occult Blood Test
Authors: Chen Chien Hua , Tsai Min Kuang , Wen Chi Pang
Published: February 2016

Goals:

To assess the association between the initial immunochemical fecal occult blood tests (FIT) and subsequent colorectal cancer, and to explore the ability of FIT to identify individuals age 40 to 49 years with a higher cancer risk.

Background:

The number of cancer cases in this age group is increasing globally and the cancers found in younger age tend to be more advanced than in older age.

Methods:

A total of 513,283 individuals had FIT as part of their self-paying medical screening program between 1994 and 2008. The initial FIT test was used. When matched with the Taiwan cancer registry, the cohort identified 2138 colorectal cancer cases. The number needed to screen (NNS) to identify 1 cancer was calculated from the reciprocal of cancer incidence cases during the study period.

Results:

One in 7 colorectal cancers above age 40 years occurred in the age group of 40 to 49 years. Individuals 40 to 49 years old with positive FIT (≥100 ng/mL) had a 3 times larger cancer risk than those 50 to 59 years old and without FIT, or double the cancer risk as those 50 to 69 years old and without FIT, with NNS at 42, 135, and 95, respectively. A similar relationship existed for the cancer incidence rate. The HR for ages 40 to 44 years or 45 to 49 years with a positive FIT was 2.3 or 5.7 times larger than the HR for ages 50 to 54 years. There was a dose-response relationship between increasing FIT values and the cancer risk for each age group, including ages 40 to 49 years.

Conclusions:

Offering FIT to individuals 40 to 49 years of age could identify higher-risk individuals earlier for follow-up colonoscopy, and could, in turn, reduce cancer mortality.
Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease
Authors: Burr Nick E. , Hull Mark A. , Subramanian Venkataraman
Published: February 2016

Goals:

To evaluate the role of folic acid supplementation in colorectal cancer (CRC) chemoprevention in patients with inflammatory bowel disease (IBD).

Background:

CRC is a serious complication of IBD. Folic acid supplementation has been shown to be chemopreventative in sporadic CRC. Patients with IBD are at risk of folate deficiency though intestinal malabsorption and also competitive inhibition by concurrent sulfasalazine use. To date, there have been several studies reporting on folic acid supplementation in patients with IBD and CRC.

Study:

We searched electronic databases for studies reporting folic acid use and CRC incidence in patients with IBD. We produced a pooled hazard ratio with 95% confidence intervals using a random-effects model. Preplanned subgroup analyses were performed to explore for any potential sources of heterogeneity.

Results:

Ten studies reporting on 4517 patients were included. We found an overall protective effect for folic acid supplementation on the development of CRC, pooled hazard ratio=0.58 (95% confidence interval, 0.37-0.80). There was low to moderate heterogeneity among studies, I
2=29.7%. Subgroup analyses suggested that folic acid use was protective in hospital-based studies, studies from North America and those that were performed before folate fortification of foods in 1998.

Conclusions:

CRC remains an important complication of IBD. Chemoprevention is an attractive strategy and folic acid as a cheap, safe, and well-tolerated supplement may have a role. Focused prospective studies are required to precisely define any potential effect.
Massachusetts Health Reform Cost Less and Was More Effective for Uninsured Individuals With Venous Thromboembolism
Authors: Kapoor Alok , Shaffer Nicholas , Hanchate Amresh , Roberts Mark , Smith Kenneth
Published: February 2016

Background:

Patients with venous thromboembolism (VTE) require access to comprehensive physician and pharmacy benefits to prevent recurrence and hemorrhage. Before 2006, Massachusetts provided these benefits through a program restricted to safety net hospitals called Free Care. Providing portable health insurance through Massachusetts health reform could improve outcomes for uninsured with VTE but its cost-effectiveness is unknown.

Methods and Results:

We constructed a Markov decision analysis model comparing our conceptualization of the Massachusetts health reform (health reform strategy) to no health reform strategy for a patient beginning warfarin for new episode of VTE. In the model, a patient may develop recurrent VTE or develop hemorrhage or stop warfarin after 6 months if no event occurs. To measure effectiveness, we analyzed laboratory data from Boston Medical Center, the largest safety net hospital in Massachusetts. Specifically, we measured the probability of having a subtherapeutic warfarin level for patients newly insured compared with those on Free Care prereform adjusting for secular trends. To calculate inpatient costs, we used the Health Care Utilization Project. We then calculated the incremental cost-effectiveness ratio for the health reform strategy adjusted to 2014 USD per quality-adjusted life-year (QALY) and performed sensitivity analyses. The health reform strategy cost less and gained more QALYs than the no health reform strategy. Our result was most sensitive to the odds that Health Reform protected against a subtherapeutic warfarin level, the cost of Health Reform, and the percentage of total health care costs attributable to VTE in Massachusetts.

Conclusion:

The health reform strategy cost less and was more effective than the no health reform strategy for patients with VTE.
An Unusual Late Recurrence of Wilms Tumor
Authors: Sudour-Bonnange Hélène , Lervat Cyril , Renaud Florence , Gauthier Hélène , Rocourt Nathalie
Published: February 2016

Wilms tumor is the most common renal tumor in children, and the 5-year survival rate is approximately 85%. The majority of relapses occur in the lung, tumor bed, and liver within 2 years of diagnosis. In this study, we describe an unusual late tumor recurrence that occurred 9.5 years after the primary diagnosis. The patient presented with a slow growing cervical lymphadenopathy. The recurrent tumor showed the same histologic features as the original tumor. The patient was treated with surgery and radiotherapy without chemotherapy. The patient remained disease free 15 months after treatment. The possible effect of treatment and other mechanisms of this late relapse are discussed.
Management Strategies in Rosai-Dorfman Disease: To Do or Not To Do
Authors: Shrirao Neha , Sethi Aditya , Mukherjee Bipasha
Published: February 2016

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is an extremely rare non-Langerhans cell histiocytosis. Orbital involvement is even rarer and may be accompanied by lymph node involvement. Treatment options range from systemic steroids and immunosuppressants to radiation and debulking. We present a rare case of bilateral orbital sinus histiocytosis with massive lymphadenopathy with cervical and circumaortic lymphadenopathy.
Low uncertainty Boltzmann constant determinations and the kelvin redefinition
Authors: Fischer J.
Published: February 2016

At its 25th meeting, the General Conference on Weights and Measures (CGPM) approved Resolution 1 ‘On the future revision of the International System of Units, the SI’, which sets the path towards redefinition of four base units at the next CGPM in 2018. This constitutes a decisive advance towards the formal adoption of the new SI and its implementation. Kilogram, ampere, kelvin and mole will be defined in terms of fixed numerical values of the Planck constant, elementary charge, Boltzmann constant and Avogadro constant, respectively. The effect of the new definition of the kelvin referenced to the value of the Boltzmann constant
k
is that the kelvin is equal to the change of thermodynamic temperature
T
that results in a change of thermal energy
kT
by 1.380 65×10
−23
 J. A value of the Boltzmann constant suitable for defining the kelvin is determined by fundamentally different primary thermometers such as acoustic gas thermometers, dielectric constant gas thermometers, noise thermometers and the Doppler broadening technique. Progress to date of the measurements and further perspectives are reported. Necessary conditions to be met before proceeding with changing the definition are given. The consequences of the new definition of the kelvin on temperature measurement are briefly outlined.
Integrating genomics into clinical pediatric oncology using the molecular tumor board at the Memorial Sloan Kettering Cancer Center
Authors: Ortiz Michael V. , Kobos Rachel , Walsh Michael , Slotkin Emily K. , Roberts Stephen , Berger Michael F. , Hameed Meera , Solit David , Ladanyi Marc , Shukla Neerav , Kentsis Alex
Published: February 2016

Background: Pediatric oncologists have begun to leverage tumor genetic profiling to match patients with targeted therapies. At the Memorial Sloan Kettering Cancer Center (MSKCC), we developed the Pediatric Molecular Tumor Board (PMTB) to track, integrate, and interpret clinical genomic profiling and potential targeted therapeutic recommendations. Procedure: This retrospective case series includes all patients reviewed by the MSKCC PMTB from July 2014 to June 2015. Cases were submitted by treating oncologists and potential treatment recommendations were based upon the modified guidelines of the Oxford Centre for Evidence Based Medicine. Results: There were 41 presentations of 39 individual patients during the study period. Gliomas, acute myeloid leukemia, and neuroblastoma were the most commonly reviewed cases. Thirty nine (87%) of the 45 molecular sequencing profiles utilized hybrid-capture targeted genome sequencing. In 30 (73%) of the 41 presentations, the PMTB provided therapeutic recommendations, of which 19 (46%) were implemented. Twenty-one (70%) of the recommendations involved targeted therapies. Three (14%) targeted therapy recommendations had published evidence to support the proposed recommendations (evidence levels 1-2), 8 (36%) recommendations had preclinical evidence (level 3), and 11 (50%) recommendations were based upon hypothetical biological rationales (level 4). Conclusions: The MSKCC PMTB enabled a clinically relevant interpretation of genomic profiling. Effective use of clinical genomics is anticipated to require new and improved tools to ascribe pathogenic significance and therapeutic actionability. Development of specific rule-driven clinical protocols will be needed for the incorporation and evaluation of genomic and molecular profiling in interventional prospective clinical trials.
CAGEd-oPOSSUM: motif enrichment analysis from CAGE-derived TSSs
Authors: Arenillas David J. , Forrest Alistair R.R. , Kawaji Hideya , Lassman Timo ,   The FANTOM Consortium, Wasserman Wyeth W. , Mathelier Anthony
Published: February 2016

With the emergence of large-scale Cap Analysis of Gene Expression (CAGE) data sets from individual labs and the FANTOM consortium, one can now analyze the cis-regulatory regions associated with gene transcription at an unprecedented level of refinement. By coupling transcription factor binding site (TFBS) enrichment analysis with CAGE-derived genomic regions, CAGEd-oPOSSUM can identify TFs that act as key regulators of genes involved in specific mammalian cell and tissue types. The webtool allows for the analysis of CAGE-derived transcription start sites (TSSs) either provided by the user or selected from ~1,300 mammalian samples from the FANTOM5 project with pre-computed TFBS predicted with JASPAR TF binding profiles. The tool helps power insights into the regulation of genes through the study of the specific usage of TSSs within specific cell types and/or under specific conditions.

Availability and implementation

The CAGEd-oPOSUM web tool is implemented in Perl, MySQL, and Apache and is available athttp://cagedop.cmmt.ubc.ca/CAGEd_oPOSSUM.

Supporting Information

Supplementary Text, Figures, and Data are available online at bioRxiv.
Bayesian analysis of normal mouse cell lineage trees allowing intra-individual, cell population specific mutation rates
Authors: Csordas Attila , Bouckaert Remco
Published: February 2016

Individual cell lineage trees are of biological and clinical importance. The Sanger Mouse Pilot Study used clonal organoid lines of endodermal origin to extract somatic base substitutions from single cells of two healthy mice. Here we applied Bayesian phylogenetics analysis using the Pilot’s 35 somatic base substitutions in order to reconstruct the two cell trees and apply relaxed clock methods allowing intra-individual, cell lineage specific mutation rates. Detailed analysis provided support for the strict clock for mouse_1 and relaxed clock for mouse_2. Interestingly, a clade of two prostate organoid lines in mouse_2 presented one outlier branch mutation rate compared to the mean rates calculated. Based on this study unbiased clock analysis has the potential to add a new, useful layer to our understanding of normal and disturbed cell lineage trees. This study is the first to apply the popular Bayesian BEAST package to individual single cell resolution data.
Structure determination of a pseudo-decagonal quasicrystal approximant by the strong-reflections approach and rotation electron diffraction
Authors: Singh Devinder , Yun Yifeng , Wan Wei , Grushko Benjamin , Zou Xiaodong , Hovmöller Sven
Published: February 2016

The structure of a complicated pseudo-decagonal (PD) quasicrystal approximant in the Al–Co–Ni alloy system, denoted as PD1, was solved by the strong-reflections approach on three-dimensional rotation electron diffraction (RED) data, using the phases from the known PD2 structure. RED shows that the PD1 crystal is primitive and orthorhombic, witha= 37.3,b= 38.8,c= 8.2 Å. However, as with other approximants in the PD series, the superstructure reflections (corresponding toc= 8.2 Å) are much weaker than those of the main reflections (corresponding toc= 4.1 Å), so it was decided to solve the PD1 structure in the smaller primitive unit cell first,i.e.with unit-cell parametersa= 37.3,b= 38.8,c= 4.1 Å and space groupPnam. A density map of PD1 was calculated from only the 15 strongest unique reflections. It contained all 31 Co/Ni atoms and many weaker peaks corresponding to Al atoms. The structure obtained from the strong-reflections approach was confirmed by applying direct methods to the complete RED data set. Successive refinement using the RED data set resulted in 108 unique atoms (31 Co/Ni and 77 Al). This is one of the most complicated approximant structures ever solved by electron diffraction. As with other approximants in the PD series, PD1 is built of characteristic 2 nm wheel clusters with fivefold rotational symmetry, which agrees with results from high-resolution electron microscopy images. The simulated electron diffraction patterns for the structure model are in good agreement with the experimental electron diffraction patterns obtained by RED.
The Comparative Analysis of Accessibility Index Value of Government Internet Financial Reporting In Indonesia
Authors: Verawaty Verawaty
Published: February 2016

The financial information through internet is called IFR (Internet Financial Reporting) which is a combination between the internet multimedia capability and capacity to communicate the financial information interactively. This study is aimed to compare the quality of financial reporting disclosures based on the accessibility of IFR on government website (e-government) by using Accessibility Index Value between two groups of samples. The study looks at Indonesia local government’s use of the internet both in provincial and municipal government. The provincial government must be more highlighted by the public so it is hypothesized it will disclose information in its e-government with better format and quality than the municipal government measured by the index which shows the ability of some citizens to access the data provided in e-government. Based on the testing results with Mann Whitney Test, the results are not significant. The majority has not emphasized the importance of increasing accountability and widening the scope of measurement and reporting systems.
The Influence of Financial Performance, Capital Structure and Macroeconomic Factors on Firm’s Value – Evidence from Textile Companies at Indonesia Stock Exchange
Authors: Jubaedah Jubaedah , Yulivan Ivan , Abdul Hadi Abdul Razak
Published: February 2016

This study aims to investigate how financial performance, capital structure and macroeconomic factors may influence a firm’s value in Indonesia textile industry.  This research is exploratory in nature involving 20 textile companies listed in Indonesia Stock Exchange (IDX). Using panel data regression, the results show that financial performance, capital structure, inflation and exchange rate are contributory factors that influence firm’s value.  The better the financial performance of a company, the higher its value will be. The study also reveals that ratio of short term debt to total assets has no significant impact on firm’s value, while there is a positive significant relationship between the ratio of long term debt to total assets and firm’s value. Interestingly, depreciation in Indonesia Rupiah and increase in inflation rate would also enhance the firm’s value. As far as Indonesian textile industry is concerned, the findings suggest that capital structure, increased financial performance, higher inflation rate and depreciating Rupiah do influence the textile company’s value.
Minor arcs, mean values, and restriction theory for exponential sums over smooth numbers
Authors: Harper Adam J.
Published: February 2016

We investigate exponential sums over those numbers ${\leqslant}x$ all of whose prime factors are ${\leqslant}y$. We prove fairly good minor arc estimates, valid whenever $\log ^{3}x\leqslant y\leqslant x^{1/3}$. Then we prove sharp upper bounds for the $p$th moment of (possibly weighted) sums, for any real $p>2$ and $\log ^{C(p)}x\leqslant y\leqslant x$. Our proof develops an argument of Bourgain, showing that this can succeed without strong major arc information, and roughly speaking it would give sharp moment bounds and restriction estimates for any set sufficiently factorable relative to its density. By combining our bounds with major arc estimates of Drappeau, we obtain an asymptotic for the number of solutions of $a+b=c$ in $y$-smooth integers less than $x$ whenever $\log ^{C}x\leqslant y\leqslant x$. Previously this was only known assuming the generalised Riemann hypothesis. Combining them with transference machinery of Green, we prove Roth’s theorem for subsets of the $y$-smooth numbers whenever $\log ^{C}x\leqslant y\leqslant x$. This provides a deterministic set, of size ${\approx}x^{1-c}$, inside which Roth’s theorem holds.