bluuebunny/crossref_metadata_2025 huggingface dataset:
Transition-Metal-Free One-Pot Tandem Synthesis of 4-Quinolone and 4H-Thiochromen-4-one Derivatives Through Sequential Nucleophilic Addition–Elimination–SNAr Reaction
Authors: Peng Jinsong , Chen Chunxia , Wang Deqiang , Sun Peng , Jia Peiyun , Yue Yixia
Published: July 2017

4-Quinolone and 4H-thiochromen-4-one derivatives are readily synthesized in a tandem one-pot manner in good to excellent yields. Starting from (Z)-β-chlorovinyl ketones, an intermolecular nucleo­philic addition of amines or sodium hydrogen sulfide to (Z)-β-chloro­vinyl ketones was followed by elimination of chlorine anion to give Z-enamine or thioenol intermediates, which can be transformed to 4-quinolone or 4H-thiochromen-4-one products through intramolecular SNAr reaction, respectively.
A New Synthesis of Pyrroles from Benzimidazolium N-Cyanomethyl Ylides and Alkyne Dipolarophiles
Authors: Caira Mino , Dumitrascu Florea , Dumitrescu Denisa , Georgescu Emilian , Draghici Constantin
Published: July 2017

A straightforward synthesis of highly functionalized pyrroles was achieved by a one-pot reaction between 3-(cyanomethyl)benzimidazolium salts and acetylenic dipolarophiles under reflux in 1,2-epoxybutane. The new pyrroles can also be obtained by a one-pot three-component reaction from substituted benzimidazoles, bromoacetonitrile, and activated acetylenes. The structures of the pyrroles were deduced by NMR spectroscopy and confirmed by X-ray crystal analysis.
The Effect of Bone Marrow Mesenchymal Stem Cells Application on Distracted Bone Quality during Rapid Rate of Distraction Osteogenesis
Authors: El Kassaby Marwa , El Kader Khaled Abd , Khamis Nahed , Al Hammoud Alaa , Talb Alaa Ben , el Hadidi YasserNabil
Published: July 2017

Distraction osteogenesis (DO) bone regenerate usually suffers from an inferior quality especially with rapid rate. This study was conducted to investigate the effect of mesenchymal stem cells (MSCs) application on different rates of distraction bone quality. Twenty-four goats were divided into group A with standard DO and group B with rapid distraction osteogenesis (RDO) both aided by MSCs. Group C with standard DO and group (D) with RDO were controls. Kruskal–Wallis test and Conover's post hoc analysis was used to evaluate significance ( p = 0.05). Histomorphometry showed a strongly significant (SS) increase ( p = 0.00036) in trabecular bone (TB) in group A (TB = 174.7 μm, SD = 33.5) and group B (TB = 166.8 μm, SD = 14) compared with group C (TB = 115.4 μm, SD = 19.6) and group D (TB = 86.1 μm, SD = 9.3). There was SS decrease ( p = 0.00093) in osteoid percentage (OP) in group A (OP = 13.4%, SD = 2) and group B (OP = 11.5%, SD = 6.5) compared with group C (OP = 27.3, SD = 3.5) and group D (OP = 26.2%, SD = 2.6). Energy dispersive X-ray showed a nonsignificant increase ( p = 0.11) in calcification (Ca2+%) in group A (Ca2+% = 17.6%, SD = 4.9) and group B (Ca2+% = 17.6%, SD = 4.3) compared with group C (Ca2+ % = 14.2%, SD = 6.7) and group D (Ca2+% = 11.5%, SD = 2.4). MSCs application improved microscopic bone quality during standard DO and RDO. However, macroscopic bone quality improvement still needs further investigation.
A Case of Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Presenting with Severe Acidosis in a 14-Month-Old Female: Evidence for Pathogenicity of a Point Mutation in the OXCT1 Gene
Authors: Zheng Daniel , Hooper Michael , Spencer-Manzon Michele , Pierce Richard
Published: July 2017

We describe a case of succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency in an otherwise healthy 14 month-old female. She presented with lethargy, tachypnea, and hyperpnea with hypoglycemia and a severe anion gap metabolic acidosis. Early management included correction of the acidosis and metabolic support with dextrose and insulin. Inborn errors of metabolism are rare outside the neonatal period. However, SCOT deficiency may present at older ages. Maintaining a high index of suspicion, immediate transfer to a pediatric intensive care unit, and prompt metabolic support are key to achieving a favorable outcome.
Neuroimaging in Neonatal Nonketotic Hyperglycinemia
Authors: Hattiholi Virupaxi , Kamate Mahesh
Published: July 2017

Nonketotic hyperglycinemia is a fatal disorder of glycine metabolism presenting with intractable epilepsy, hypotonia, and developmental delay in infancy. Diagnostic tests,such as cerebrospinal fluid glycine estimation and genetic diagnostic methods, are not widely available in developing countries and hence many cases are missed or wrongly diagnosed. The magnetic resonance imaging features, such as abnormal signal intensity in the dorsal pons, midbrain, central tegmental tract, cerebral peduncle, and posterior limb of the internal capsule indicate an important clue to the possibility of the disease and help in guiding the treating neonatologist.
Psychological Consequences of Maxillofacial Trauma in the Indian Population: A Preliminary Study
Authors: Krishnan Balasubramanian , Rajkumar Ravi Philip
Published: July 2017

The aim of this article is to identify the prevalence of posttraumatic psychological symptoms following maxillofacial trauma among an Indian population sample and assess changes in these symptoms over a period of time. Forty-eight adult patients were assessed within 2 weeks of injury with two follow-up visits (4–6 weeks and 12–14 weeks). Patients were administered three self-reporting questionnaires in local language (GHQ-12; HADS; TSQ) on all occasions. Relevant sociodemographic and clinical data were obtained. Forty patients were included in the final analysis. Emotional distress was present in nine participants and five participants satisfied the TSQ criteria for a diagnosis of stress disorder. Anxiety and depression were observed in 10 and 4 patients, respectively. Characteristics associated with abnormal high scores included substance abuse, low education and income levels, facial scars, and complications needing additional intervention. These findings reveal the abnormal psychological response to maxillofacial trauma in immediate and follow-up periods. The use of such screening tools can be considered by the maxillofacial surgeon for early identification of psychological symptoms and referral to the psychiatrist.
Formation of 238U16O and 238U18O observed by time-resolved emission spectroscopy subsequent to laser ablation
Authors: Weisz David G. , Crowhurst Jonathan C. , Siekhaus Wigbert J. , Rose Timothy P. , Koroglu Batikan , Radousky Harry B. , Zaug Joseph M. , Armstrong Michael R. , Isselhardt Brett H. , Savina Michael R. , Azer Magdi , Finko Mikhail S. , Curreli Davide
Published: July 2017

We have measured vibronic emission spectra of an oxide of uranium formed after laser ablation of the metal in gaseous oxygen. Specifically, we have measured the time-dependent relative intensity of a band located at approximately 593.6 nm in 16O2. This band grew in intensity relative to neighboring atomic features as a function time in an oxygen environment but was relatively invariant with time in argon. In addition, we have measured the spectral shift of this band in an 18O2 atmosphere. Based on this shift, and by comparison with earlier results obtained from free-jet expansion and laser excitation, we can confirm that the oxide in question is UO, consistent with recent reports based on laser ablation in 16O2 only.
The interplay of blocking properties with charge and potential redistribution in thin carbon-doped GaN on n-doped GaN layers
Authors: Koller Christian , Pobegen Gregor , Ostermaier Clemens , Huber Martin , Pogany Dionyz
Published: July 2017

In carbon-doped GaN (GaN:C) buffers used in a GaN-on-Si technology, the buffer is embedded in between transition and channel layers. This makes the analysis of buffer properties difficult due to e.g., carrier injection from or potential drop at these adjacent layers. Here, we analyze capacitance- and current-voltage characteristics of 200–300 nm thick GaN:C ([C] = 1019 cm−3) layers which are embedded between a top metal electrode and bottom n-doped GaN (n-GaN). Such structures allow a better potential control in GaN:C and thus determination of the band diagram quantitatively. The accumulation of negative charge (concentration up to 6 × 1017 cm−3) with bias is observed in GaN:C at both polarities. For biases Vappl < +1.7 V at the top electrode, negative charges accumulate in GaN:C near to its interface with n-GaN so that GaN:C exhibits no potential drop and blocks leakage current. For Vappl > +1.7 V, accumulated negative charges in GaN:C raise an energy barrier of ∼1.1 eV for electron injection from n-GaN to GaN:C. This causes a potential drop in GaN:C leading to a significant leakage current increase. The Fermi level pinning in GaN:C at a commonly referred acceptor at EV + 0.7(±0.2) eV is extracted only from electrostatic considerations. The occupancy change of carbon acceptors is attributed to trapping processes where the dislocation-related conductive paths are supposed to be involved in carrier transport from the top metal electrode to the carbon defect.
Oscillatory device for use with linear tribometer, for tribological evaluation of biomaterials
Authors: Athayde J. N. , Siqueira C. J. M. , Kuromoto N. K. , Cambraia H. N.
Published: July 2017

Orthopedic implants still have limitations regarding their durability, despite being in use for over fifty years. Particles arising from wear due to the relative motion of their surfaces remain responsible for aseptic failure. This paper presents a device to be coupled with a reciprocal linear tribometer to reproduce the ex vivo wear of biomaterials, allowing the measurement of force and coefficient of friction. The device consists of a structure connected to the tribometer that transforms its reciprocal linear motion into one that is oscillatory for the mechanical assembly that contains the samples to test the desired biomaterials. The tribological pair used for testing consisted of Ultra High Molecular Weight Polyethylene (UHMWPE) in conjunction with the austenitic stainless steel AISI 316L in dry lubrication. The results showed that the values of the coefficient of friction in the linear mode and oscillatory mode and the UHMWPE life curve in the oscillatory mode were consistent with those cited in the literature for tests in a dry lubrication environment. Moreover, the UHMWPE sample life curve showed a reduction in the wear rate that can be explained by the preponderance of a wear mechanism over the others. The volumetric wear showed an increase with the number of cycles.
Design of octahedral spherical hohlraum for CH Rev5 ignition capsule
Authors: Cao Hui , Chen Yao-Hua , Zhai Chuanlei , Zheng Chunyang , Lan Ke
Published: July 2017

In this paper, we design an octahedral spherical Au hohlraum for CH Rev5 ignition capsule [S. W. Haan et al., Phys. Plasmas 18, 051001 (2011)] by using the initial design method and two-dimensional (2D) simulations, and we investigate its laser entrance hole (LEH) closure and laser-plasma instabilities (LPI) by using a spherical hohlraum with two different-size LEHs via 2D simulations. The designed spherical hohlraum with RH=5 RC, RL=1.2 mm, and RL*=2RL requires an ignition laser pulse of 1.92 MJ in energy and 670 TW in peak power, where RH, RC, RL, and RL* are radii of the spherical hohlraum, capsule, LEH, and the cylindrical LEH outer ring, respectively. From 2D simulations, the closure and opening up of LEH are clearly obtained. The LEH closure and its rate are strongly connected to the radiation pulse, while the LEH opening-up and its rate are strongly connected to the laser pulse. The smallest radius of LEH during closure is 0.6 mm before opening up, which leaves enough room for arranging the laser beams with a radius of 0.5 mm in our design. By using a post-process code for LPI, a relatively high stimulated Brillouin scattering fraction and a very low stimulated Raman scattering fraction are predicted, which may be due to the neglection of three-dimensional density gradients of the ablative flow along the laser transportation in 2D simulations. This work provides the energy and power references for the future ignition laser facility which uses octahedral spherical hohlraums as ignition targets.
Intrinsically disordered chromatin protein NUPR1 binds to the C-terminal region of Polycomb RING1B
Authors: Santofimia-Castaño Patricia , Rizzuti Bruno , Pey Ángel L. , Soubeyran Philippe , Vidal Miguel , Urrutia Raúl , Iovanna Juan L. , Neira José L.
Published: July 2017

Significance

We describe the interaction between an intrinsically disordered protein (IDP), NUPR1, and the well-folded C-terminal region of RING1B protein of the Polycomb complex, involving residues Ala33 and Thr68 of the IDP. These observations are significant because they raise the possibility that NUPR1 aids the function of the members of the Polycomb complex, playing an active role in carcinogenesis.
Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain
Authors: Kato Yuri , Hiasa Miki , Ichikawa Reiko , Hasuzawa Nao , Kadowaki Atsushi , Iwatsuki Ken , Shima Kazuhiro , Endo Yasuo , Kitahara Yoshiro , Inoue Tsuyoshi , Nomura Masatoshi , Omote Hiroshi , Moriyama Yoshinori , Miyaji Takaaki
Published: July 2017

Significance

Although the incidence of chronic pain is estimated at 20–25% worldwide, optimal drug treatment regimens with few side effects have yet to be developed. In this study, we demonstrated that clodronate is a potent and selective inhibitor of vesicular ATP release that attenuates neuropathic and inflammatory pain unrelated to bone abnormalities. Clodronate was more effective and associated with comparatively fewer side effects than existing drugs. Thus, the nonopioid agent clodronate may represent a unique treatment strategy for chronic pain via inhibition of vesicular ATP release, suggesting that clodronate may be effective in the treatment of several diseases involving purinergic chemical transmission, including inflammatory diseases, diabetes, and neurological disorders. Our study identifies a transporter-targeted analgesic drug.
Stabilization of F-actin by tropomyosin isoforms regulates the morphology and mechanical behavior of red blood cells
Authors: Sui Zhenhua , Gokhin David S. , Nowak Roberta B. , Guo Xinhua , An Xiuli , Fowler Velia M.
Published: July 2017

The short F-actins in the red blood cell (RBC) membrane skeleton are coated along their lengths by an equimolar combination of two tropomyosin isoforms, Tpm1.9 and Tpm3.1. We hypothesized that tropomyosin’s ability to stabilize F-actin regulates RBC morphology and mechanical properties. To test this, we examined mice with a targeted deletion in alternatively spliced exon 9d of Tpm3 (Tpm3/9d–/–), which leads to absence of Tpm3.1 in RBCs along with a compensatory increase in Tpm1.9 of sufficient magnitude to maintain normal total tropomyosin content. The isoform switch from Tpm1.9/Tpm3.1 to exclusively Tpm1.9 does not affect membrane skeleton composition but causes RBC F-actins to become hyperstable, based on decreased vulnerability to latrunculin-A–induced depolymerization. Unexpectedly, this isoform switch also leads to decreased association of Band 3 and glycophorin A with the membrane skeleton, suggesting that tropomyosin isoforms regulate the strength of F-actin-to-membrane linkages. Tpm3/9d–/–mice display a mild compensated anemia, in which RBCs have spherocytic morphology with increased osmotic fragility, reduced membrane deformability, and increased membrane stability. We conclude that RBC tropomyosin isoforms directly influence RBC physiology by regulating 1) the stability of the short F-actins in the membrane skeleton and 2) the strength of linkages between the membrane skeleton and transmembrane glycoproteins.
Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
Authors: Long Kimberly R. , Shipman Katherine E. , Rbaibi Youssef , Menshikova Elizabeth V. , Ritov Vladimir B. , Eshbach Megan L. , Jiang Yu , Jackson Edwin K. , Baty Catherine J. , Weisz Ora A.
Published: July 2017

Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to maintain glomerulotubular balance. PT cells in culture up-regulate endocytic capacity in response to acute changes in fluid shear stress (FSS); however, it is not known whether GFR modulates PT endocytosis to enable maximally efficient uptake of filtered proteins in vivo. Here, we show that cells cultured under continuous FSS develop an expanded apical endocytic pathway and increased endocytic capacity and lysosomal biogenesis. Furthermore, endocytic capacity in fully differentiated cells is rapidly modulated by changes in FSS. PT cells exposed to continuous FSS also acquired an extensive brush border and basolateral membrane invaginations resembling those observed in vivo. Culture under suboptimal levels of FSS led to intermediate phenotypes, suggesting a threshold effect. Cells exposed to FSS expressed higher levels of key proteins necessary for PT function, including ion transporters, receptors, and membrane-trafficking machinery, and increased adenine nucleotide levels. Inhibition of the mechanistic target of rapamycin (mTOR) using rapamycin prevented the increase in cellular energy levels, lysosomal biogenesis, and endocytic uptake, suggesting that these represent a coordinated differentiation program. In contrast, rapamycin did not prevent the FSS-induced increase in Na+/K+-ATPase levels. Our data suggest that rapid tuning of the endocytic response by changes in FSS may contribute to glomerulotubular balance in vivo. Moreover, FSS provides an essential stimulus in the differentiation of PT cells via separate pathways that up-regulate endocytosis and ion transport capacity. Variations in FSS may also contribute to the maturation of PT cells during kidney development and during repair after kidney injury.
FOLD: a method to optimize power in meta-analysis of genetic association studies with overlapping subjects
Authors: Kim Emma E , Lee Seunghoon , Lee Cue Hyunkyu , Oh Hyunjung , Song Kyuyoung , Han Buhm
Published: July 2017

Motivation

In genetic association studies, meta-analyses are widely used to increase the statistical power by aggregating information from multiple studies. In meta-analyses, participating studies often share the same individuals due to the shared use of publicly available control data or accidental recruiting of the same subjects. As such overlapping can inflate false positive rate, overlapping subjects are traditionally split in the studies prior to meta-analysis, which requires access to genotype data and is not always possible. Fortunately, recently developed meta-analysis methods can systematically account for overlapping subjects at the summary statistics level.

Results

We identify and report a phenomenon that these methods for overlapping subjects can yield low power. For instance, in our simulation involving a meta-analysis of five studies that share 20% of individuals, whereas the traditional splitting method achieved 80% power, none of the new methods exceeded 32% power. We found that this low power resulted from the unaccounted differences between shared and unshared individuals in terms of their contributions towards the final statistic. Here, we propose an optimal summary-statistic-based method termed as FOLD that increases the power of meta-analysis involving studies with overlapping subjects.

Availability and implementation

Our method is available at http://software.buhmhan.com/FOLD.

Supplementary information

Supplementary data are available at Bioinformatics online.
Uromodulin–SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells
Authors: Yanagihara Sae , Kanaya Takashi , Fukuda Shinji , Nakato Gaku , Hanazato Misaho , Wu Xue-Ru , Yamamoto Naoyuki , Ohno Hiroshi
Published: July 2017

Bacterial access to the gut immune system is a crucial process to promote host immune responses. The probiotic L-92 strain of Lactobacillus acidophilus exerts anti-allergic immunomodulatory effects upon oral administration in mice. Here, we show that microfold cells (M cells) are responsible for L-92 internalization for evoking L-92-mediated immune responses. L-92 specifically bound to uromodulin, a glycosylphosphatidylinositol-anchored protein expressed exclusively on M cells among intestinal epithelial cells. Internalization of L-92 into M cells was significantly reduced in uromodulin-deficient (Umod−/−) mice compared to Umod+/+ mice. Furthermore, the binding of L-92 to uromodulin was significantly decreased after removal of surface layer protein A (SlpA) from the bacteria. Our study thus revealed a crucial role of uromodulin on the M-cell surface for the uptake of SlpA-positive lactic acid bacteria into M cells, possibly leading to subsequent delivery of the bacteria to dendritic cells closely associated with M cells for immunomodulation. Our study also shed light on the possibility that SlpA and uromodulin could be used as vehicle and target, respectively, for efficient mucosal vaccine delivery.
In Vitro Compatibility of Contact Lenses With Corneal Epithelial Cells
Authors: Vijay Ajay K. , Fadli Zohra , Lakkis Carol , Coles-Brennan Chantal , Willcox Mark D. P.
Published: July 2017

Purpose:

To determine the interaction of contact lenses of different materials with corneal epithelial cells grown in tissue culture.

Methods:

Two different corneal epithelial cell lines were grown to confluence in culture media. Two hydrogel contact lenses with and without polyvinylpyrrolidone (PVP) {1-DAY ACUVUE MOIST (1-Day ACUVUE [hydrogel lenses]) and a silicone hydrogel contact lens, AIR OPTIX NIGHT & DAY} were removed from their blister packs, washed in phosphate-buffered saline, and applied to the cells. After exposure for 24 hr at 37°C, lenses were removed, and the corneal cells and supernatants processed. Supernatants from the cell assays were used to quantify the amount of 17 different cytokines that were produced using a multiplex bead assay. Cells were stained to assess amount of cell death (apoptosis or necrosis) or stained to determine the level of mitochondrial activity. Stimulants of necrotic death (latex) or apoptotic death (sorbitol) were used as positive controls.

Results:

Cells produced cytokines during normal growth. Exposure of cells to the hydrogel lenses resulted in only minimal changes to normal production of cytokines, but latex or sorbitol produced the most change. Exposure of the cells to all three lenses caused 4% to 23% reduction in mitochondrial activity, whereas exposure to the positive controls caused 71% to 98% reduction in mitochondrial activity. Exposure of the corneal epithelial cells to contact lenses produced minimal morphological changes, whereas exposure to latex or sorbitol produced significant changes to the human corneal epithelial cell line.

Conclusions:

Exposure of corneal epithelial cells to contact lenses had minimal impact on their physiology. There was no difference in epithelial cell responses to hydrogel with or without PVP compared with the silicone hydrogel contact lens.
Osteoarticular Infections Caused by Streptococcus pneumoniae in Children in the Post–Pneumococcal Conjugate Vaccine Era
Authors: Olarte Liset , Romero Jose , Barson William , Bradley John , Lin Philana Ling , Givner Laurence , Tan Tina , Hoffman Jill , Hultén Kristina G. , Mason Edward O. , Kaplan Sheldon L.
Published: July 2017

Background:

Pneumococcal osteoarticular infections (OAIs) are an uncommon manifestation of invasive pneumococcal disease (IPD). We describe the demographic characteristics, hospitalization rate, serotype distribution and antibiotic susceptibility of children with pneumococcal OAI over a 16-year period.

Methods:

We identified patients ≤18 years old with pneumococcal OAI at 8 children’s hospitals in the United States (2000–2015). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory.

Results:

We identified 97 (3.3%) patients with pneumococcal OAI out of 2943 patients with IPD. Over 60% of the children were <2 years old. Septic arthritis (56.7%, 55/97) was the most common pneumococcal OAI, followed by osteomyelitis (25.8%, 25/97) and septic arthritis with concomitant osteomyelitis (17.5%, 17/97). Hospitalization for pneumococcal OAI overall decreased from 6.8 [95% confidence interval (CI): 5.2–8.6] to 4.4 (95% CI: 3.0–6.3) per 100,000 admissions from 2000–2009 to 2010–2015 (–35%, P = 0.05). Hospitalization for pneumococcal OAI caused by PCV13 serotypes decreased from 4.6 (95% CI: 3.4–6.2) to 0.9 (95% CI: 0.3–1.9) per 100,000 admissions from 2000–2009 to 2010–2015 (–87%, P < 0.0001). Overall, 12% of isolates had a penicillin minimal inhibitory concentration> 2 µg/mL, 3% a ceftriaxone minimal inhibitory concentration> 1 µg/mL and 15% were clindamycin resistant; these proportions remained unchanged after the introduction of PCV13. Serotypes 19A and 35B were responsible for penicillin and ceftriaxone nonsusceptible isolates in 2010–2015.

Conclusions:

Pneumococcal OAI represents 3% of all IPD, affecting mainly healthy infants and young children. Hospitalization for pneumococcal OAI caused by PCV13 serotypes dramatically decreased (–87%) after the introduction of PCV13.
Marked Underreporting of Pertussis Requiring Hospitalization in Infants as Estimated by Capture–Recapture Methodology, Germany, 2013–2015
Authors: Schielke Anika , Takla Anja , von Kries Rüdiger , Wichmann Ole , Hellenbrand Wiebke
Published: July 2017

Background:

In Germany, pertussis became notifiable in eastern federal states in 2002 and nationwide in March 2013. Infants are at greatest risk for severe disease, with a high proportion requiring hospitalization. We implemented enhanced hospital-based surveillance to estimate the incidence of pertussis requiring hospitalization among infants in Germany and to determine the proportion of infants hospitalized with pertussis too young to have been vaccinated.

Methods:

Enhanced surveillance was implemented within a nationwide hospital surveillance network (ESPED). We defined cases as children less than 1 year of age hospitalized due to laboratory-confirmed pertussis with disease onset from 01/07/2013-30/06/2015. We matched cases to those ascertained in the national statutory notification system, and estimated incidence using capture-recapture methodology.

Results:

The estimated annual incidence of pertussis requiring hospitalization in infants was 52/100,000 infants (95% confidence interval [CI] 48-57/100,000), with 39% under-reporting to the national notification system. During the two epidemiologic years under-reporting decreased from 46% to 32% and was lower in eastern than western federal states (21% vs. 40%). Within ESPED, 154 of 240 infants (64%) were younger than or still at the age recommended for the first vaccine dose; 55 (23%) could have received one or more vaccine doses. Median length of hospitalization was 9 days (IQR 5-13 days) and 18% required intensive care treatment.

Conclusions:

Our study revealed a high burden of pertussis in infants with marked under-reporting, especially in western federal states where notification was only recently established. Strategies for the prevention of severe pertussis.
Effect of E-Bike Versus Bike Commuting on Cardiorespiratory Fitness in Overweight Adults: A 4-Week Randomized Pilot Study
Authors: Höchsmann Christoph , Meister Steffen , Gehrig Damiana , Gordon Elisa , Li Yanlei , Nussbaumer Monique , Rossmeissl Anja , Schäfer Juliane , Hanssen Henner , Schmidt-Trucksäss Arno
Published: July 2017

Objective:

To assess if active commuting with an electrically assisted bicycle (e-bike) during a 4-week period can induce increases in cardiorespiratory fitness measured as peak oxygen uptake (V̇o
2peak) in untrained, overweight individuals, and if these changes are comparable with those induced by a conventional bicycle.

Design:

Four-week randomized pilot study.

Setting:

Controlled laboratory.

Participants:

Thirty-two volunteers (28 men) participated. Seventeen {median age 37 years [interquartile range (IQR) 34, 45], median body mass index [BMI] 29 kg/m2 [IQR 27, 31]} were randomized to the E-Bike group and 15 [median age 43 years (IQR 38, 45), median BMI 28 kg/m2 (IQR 26, 29)] to the Bike group.

Interventions:

Participants in both groups were instructed to use the bicycle allocated to them (e-bike or conventional bicycle) for an active commute to work in the Basel (Switzerland) area at a self-chosen speed on at least 3 days per week during the 4-week intervention period.

Main Outcome Measures:

V̇o
2peak was assessed before and after the intervention in an all-out exercise test on a bicycle ergometer.

Results:

V̇o
2peak increased by an average of 3.6 mL/(kg·min) [SD 3.6 mL/(kg·min)] in the E-Bike group and by 2.2 mL/(kg·min) [SD 3.5 mL/(kg·min)] in the Bike group, with an adjusted difference between the 2 groups of 1.4 mL/(kg·min) [95% confidence interval, −1.4-4.1; P = 0.327].

Conclusions:

E-bikes may have the potential to improve cardiorespiratory fitness similar to conventional bicycles despite the available power assist, as they enable higher biking speeds and greater elevation gain.
Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier
Authors: Rigo Jacques , Hascoët Jean‐Michel , Billeaud Claude , Picaud Jean‐Charles , Mosca Fabio , Rubio Amandine , Saliba Elie , Radkë Michaël , Simeoni Umberto , Guillois Bernard , de Halleux Virginie , Jaeger Jonathan , Ameye Laurent , Hays Nicholas P. , Spalinger Johannes
Published: July 2017

Objectives:

The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium‐chain triglycerides and docosahexaenoic acid.

Methods:

In this controlled, multicenter, double‐blind study, a sample of preterm infants ⩽32 weeks or ⩽1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = –1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored.

Results:

Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g · kg−1 · day−1 (cHMF) between study days 1 and 21 (D1–D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight‐for‐age z score at D21 and HC‐for‐age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre‐albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ⩽ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events.

Conclusions:

nHMF providing more protein and fat compared to a control fortifier is safe, well‐tolerated, and improves the weight gain of preterm infants.
Sociodemographic Predictors of Anal Cancer Screening and Follow-up in Human Immunodeficiency Virus–Infected Individuals
Authors: Wells Jessica S. , Holstad Marcia M. , Watkins Bruner Deborah
Published: July 2017

Background:

Anal cancer in the United States is generally rare; however, human immunodeficiency virus (HIV)–infected individuals are 28 times more likely to be given a diagnosis of anal cancer than the general population.

Objective:

The aim of this study was to examine the rates and sociodemographic predictors of anal cancer screening and follow-up anoscopy in a sample of HIV-infected individuals.

Methods:

Data for this study (n = 200) were derived from a retrospective chart review of randomly selected HIV-infected individuals. Data analyses included Pearson's correlation coefficient statistic to examine bivariate associations and logistic regression modeling for prediction of anal Papanicolaou test screening and follow-up anoscopy.

Results:

Screening rates and follow-up after an abnormal anal Pap test were low. Women were less likely to be screened for anal cancer (odds ratio [OR], 0.244; P = .007). Men who have sex with men were almost 4 times more likely to be screened for anal cancer (OR, 3.7; P = .02). Men who have sex with men were 6 times more likely to have follow-up after an abnormal anal Pap test compared with heterosexual men or women of any sexual orientation (OR, 6.88; P = .002).

Conclusions:

High-risk groups for anal cancer should be targeted for preventative measures as part of a cancer prevention plan to decrease the personal and clinical burden associated with anal cancer.

Implications for Practice:

Cancer prevention is a multistep process that requires screening and follow-up efforts, where healthcare providers play a vital role in these efforts. Findings from this study can inform strategies to improve screening and follow-up rates in HIV-infected individuals.
Cervical spine evaluation and clearance in the intoxicated patient: A prospective Western Trauma Association Multi-Institutional Trial and Survey
Authors: Martin Matthew J. , Bush Lisa D. , Inaba Kenji , Byerly Saskya , Schreiber Martin , Peck Kimberly A. , Barmparas Galinos , Menaker Jay , Hazelton Joshua P. , Coimbra Raul , Zielinski Martin D. , Brown Carlos V.R. , Ball Chad G. , Cherry-Bukowiec Jill R. , Burlew Clay Cothren , Dunn Julie , Minshall C. Todd , Carrick Matthew M. , Berg Gina M. , Demetriades Demetrios , Long William
Published: July 2017

BACKGROUND

Intoxication often prevents clinical clearance of the cervical spine (Csp) after trauma leading to prolonged immobilization even with a normal computed tomography (CT) scan. We evaluated the accuracy of CT at detecting clinically significant Csp injury, and surveyed participants on related opinions and practice.

METHODS

A prospective multicenter study (2013–2015) at 17 centers. All adult blunt trauma patients underwent structured clinical examination and imaging including a Csp CT, with follow-up thru discharge. alcohol- and drug-intoxicated patients (TOX+) were identified by serum and/or urine testing. Primary outcomes included the incidence and type of Csp injuries, the accuracy of CT scan, and the impact of TOX+ on the time to Csp clearance. A 36-item survey querying local protocols, practices, and opinions in the TOX+ population was administered.

RESULTS

Ten thousand one hundred ninety-one patients were prospectively enrolled and underwent CT Csp during the initial trauma evaluation. The majority were men (67%), had vehicular trauma or falls (83%), with mean age of 48 years, and mean Injury Severity Score (ISS) of 11. The overall incidence of Csp injury was 10.6%. TOX+ comprised 30% of the cohort (19% EtOH only, 6% drug only, and 5% both). TOX+ were significantly younger (41 years vs. 51 years; p < 0.01) but with similar mean Injury Severity Score (11) and Glasgow Coma Scale score (13). The TOX+ cohort had a lower incidence of Csp injury versus nonintoxicated (8.4% vs. 11.5%; p < 0.01). In the TOX+ group, CT had a sensitivity of 94%, specificity of 99.5%, and negative predictive value (NPV) of 99.5% for all Csp injuries. For clinically significant injuries, the NPV was 99.9%, and there were no unstable Csp injuries missed by CT (NPV, 100%). When CT Csp was negative, TOX+ led to longer immobilization versus sober patients (mean, 8 hours vs. 2 hours; p < 0.01), and prolonged immobilization (>12 hrs) in 25%. The survey showed marked variations in protocols, definitions, and Csp clearance practices among participating centers, although 100% indicated willingness to change practice based on these data.

CONCLUSION

For intoxicated patients undergoing Csp imaging, CT scan was highly accurate and reliable for identifying clinically significant spine injuries, and had a 100% NPV for identifying unstable injuries. CT-based clearance in TOX+ patients appears safe and may avoid unnecessary prolonged immobilization. There was wide disparity in practices, definitions, and opinions among the participating centers.

LEVEL OF EVIDENCE

Diagnostic tests or criteria, level II.
Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation
Authors: Cantrelle Christelle , Legeai Camille , Latouche Aurélien , Tuppin Philippe , Jasseron Carine , Sebbag Laurent , Bastien Olivier , Dorent Richard
Published: July 2017

Background

Heart allocation systems are usually urgency-based, offering grafts to candidates at high risk of waitlist mortality. In the context of a revision of the heart allocation rules, we determined observed predictors of 1-year waitlist mortality in France, considering the competing risk of transplantation, to determine which candidate subgroups are favored or disadvantaged by the current allocation system.

Methods

Patients registered on the French heart waitlist between 2010 and 2013 were included. Cox cause-specific hazards and Fine and Gray subdistribution hazards were used to determine candidate characteristics associated with waitlist mortality and access to transplantation.

Results

Of the 2053 candidates, 7 variables were associated with 1-year waitlist mortality by the Fine and Gray method including 4 candidate characteristics related to heart failure severity (hospitalization at listing, serum natriuretic peptide level, systolic pulmonary artery pressure, and glomerular filtration rate) and 3 characteristics not associated with heart failure severity but with lower access to transplantation (blood type, age, and body mass index). Observed waitlist mortality for candidates on mechanical circulatory support was like that of others.

Conclusions

The heart allocation system strongly modifies the risk of pretransplant mortality related to heart failure severity. An in-depth competing risk analysis is therefore a more appropriate method to evaluate graft allocation systems. This knowledge should help to prioritize candidates in the context of a limited donor pool.
Caryolan-1-ol, an antifungal volatile produced byStreptomycesspp., inhibits the endomembrane system of fungi
Authors: Cho Gyeongjun , Kim Junheon , Park Chung Gyoo , Nislow Corey , Weller David M. , Kwak Youn-Sig
Published: July 2017

Streptomycesspp. have the ability to produce a wide variety of secondary metabolites that interact with the environment. This study aimed to discover antifungal volatiles from the genusStreptomycesand to determine the mechanisms of inhibition. Volatiles identified fromStreptomycesspp. included three major terpenes, geosmin, caryolan-1-ol and an unknown sesquiterpene. antiSMASH and KEGG predicted that the volatile terpene synthase gene clusters occur in theStreptomycesgenome. Growth inhibition was observed when fungi were exposed to the volatiles. Biological activity of caryolan-1-ol has previously not been investigated. Fungal growth was inhibited in a dose-dependent manner by a mixture of the main volatiles, caryolan-1-ol and the unknown sesquiterpene, fromStreptomycessp. S4–7. Furthermore, synthesized caryolan-1-ol showed similar antifungal activity. Results of chemical-genomics profiling assays showed that caryolan-1-ol affected the endomembrane system by disrupting sphingolipid synthesis and normal vesicle trafficking in the fungi.
Early life manipulations of vasopressin-family peptides alter vocal learning
Authors: Baran Nicole M. , Peck Samantha C. , Kim Tabitha H. , Goldstein Michael H. , Adkins-Regan Elizabeth
Published: July 2017

Vocal learning from social partners is crucial for the successful development of communication in a wide range of species. Social interactions organize attention and enhance motivation to learn species-typical behaviour. However, the neurobiological mechanisms connecting social motivation and vocal learning are unknown. Using zebra finches (
Taeniopygia guttata
), a ubiquitous model for vocal learning, we show that manipulations of nonapeptide hormones in the vasopressin family (arginine vasotocin, AVT) early in development can promote or disrupt both song and social motivation. Young male zebra finches, like human infants, are socially gregarious and require interactive feedback from adult tutors to learn mature vocal forms. To investigate the role of social motivational mechanisms in song learning, in two studies, we injected hatchling males with AVT or Manning compound (MC, a nonapeptide receptor antagonist) on days 2–8 post-hatching and recorded song at maturity. In both studies, MC males produced a worse match to tutor song than controls. In study 2, which experimentally controlled for tutor and genetic factors, AVT males also learned song significantly better compared with controls. Furthermore, song similarity correlated with several measures of social motivation throughout development. These findings provide the first evidence that nonapeptides are critical to the development of vocal learning.
OPUS-CSF: A C-atom-based Scoring Function for Ranking Protein Structural Models
Authors: Xu Gang , Ma Tianqi , Zang Tianwu , Wang Qinghua , Ma Jianpeng
Published: July 2017

We report aC-atom-basedscoringfunction, named OPUS-CSF, for ranking protein structural models. Rather than using traditional Boltzmann formula, we built a scoring function (CSF score) based on the native distributions (analyzed through entire PDB) of coordinate components of mainchain C atoms on selected residues of peptide segments of 5, 7, 9, and 11 residues in length. In testing OPUS-CSF on decoy recognition, it maximally recognized 257 native structures out of 278 targets in 11 commonly used decoy sets, significantly more than other popular all-atom empirical potentials. The average correlation coefficient with TM-score was also comparable with those of other potentials. OPUS-CSF is a highly coarse-grained scoring function, which only requires input of partial mainchain information, and very fast. Thus it is suitable for applications at early stage of structural building.
Mono-ubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes
Authors: Giovannone Adrian J. , Reales Elena , Bhattaram Pallavi , Fraile-Ramos Alberto , Weimbs Thomas
Published: July 2017

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes / lysosomes though how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes mono - ubiquitination in a conserved polybasic domain. Stx3 present at the basolateral – but not the apical - plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs) and excreted in exosomes. A non - ubiquitinatable mutant of Stx3 (Stx3 - 5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV / exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3 - 5R mutant acts as a dominant - negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3 - 5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploit this pathway for virion excretion.
unitas: the universal tool for annotation of small RNAs
Authors: Gebert Daniel , Hewel Charlotte , Rosenkranz David
Published: July 2017

Background

Next generation sequencing is a key technique in small RNA biology research that has led to the discovery of functionally different classes of small non-coding RNAs in the past years. However, reliable annotation of the extensive amounts of small non-coding RNA data produced by high-throughput sequencing is time-consuming and requires robust bioinformatics expertise. Moreover, existing tools have a number of shortcomings including a lack of sensitivity under certain conditions, limited number of supported species or detectable sub-classes of small RNAs.

Results

Here we introduce unitas, an out-of-the-box ready software for complete annotation of small RNA sequence datasets, supporting the wide range of species for which non-coding RNA reference sequences are available in the Ensembl databases (currently more than 800). unitas combines high quality annotation and numerous analysis features in a user-friendly manner. A complete annotation can be started with one simple shell command, making unitas particularly useful for researchers not having access to a bioinformatics facility. Noteworthy, the algorithms implemented in unitas are on par or even outperform comparable existing tools for small RNA annotation that base on available ncRNA sequence information.

Conclusions

unitas brings together annotation and analysis features that hitherto required the installation of numerous different bioinformatics tools which can pose a challenge for the non-expert user. With this, unitas overcomes the problem of read normalization. Moreover, the high quality of sequence annotation and analysis, paired with the ease of use, make unitas a valuable tool for researchers in all fields connected to small RNA biology.
Unexpected Properties of Short Genomic Tandem Repeats
Authors: Glotova Irina , Molla Michael , Delcher Arthur L. , Kasif Simon
Published: July 2017

Length polymorphisms in genomic short tandem repeats have been implicated in a variety of diseases, most notably human neurodegenerative disorders. Expansions of tandem repeats are also associated with genomic instability in cancer. Our previous study of length-3 tandem repeats uncovered a surprising pattern in the length distribution of certain such repeats in the non-coding regions of the human reference genome: a bias towards repeats of length 3n- 1, (n> 3). That is, the observed frequency of repeats of this length in the human genome is higher than expected by chance based on the frequency of shorter repeats.

We have hypothesized that this pattern may be a general property of genomic DNA. If true, this could have implications with regard to the dynamics of repeat expansion generally. To test this hypothesis, we have analyzed the genomic sequences of a broad range of eukaryotic organisms as well as several complete human genomes and obtained a number of thought provoking results. We establish that this unexpected elevation in frequency of 3n- 1 long repeats is statistically significant. We also expanded this analysis to different classes of genomic regions and tandem repeats of length four and five. The specific pattern was found in 13 of the 20 organisms analyzed, including all chordate and insect genomes tested. The bias pattern, however, was not confined to a single branch of the evolutionary tree. For some genomes, such asDrosophila melanogaster, the repeat bias surprisingly was also identified in exons. The pattern is present in both small and large genomes. A similar pattern was also found in tetranucleotide and pentanucleotide repeats in the human genome. Another surprising property was identified for the flanking GC content for triplet repeats of length 3n. These findings indicate a puzzling new genomic phenomenon with possible evolutionary and disease-related implications.