bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese herbal medicine for functional dyspepsia: systematic review of systematic reviews
Authors: Chu Michael H. K. , Wu Irene X. Y. , Ho Robin S. T. , Wong Charlene H. L. , Zhang Anthony L. , Zhang Yan , Wu Justin C. Y. , Chung Vincent C. H.
Published: July 2018

Background:

Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM.

Method:

We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs.

Results:

A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported.

Conclusion:

CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future.
Clinico-epidemiology, malacology and community awareness of Schistosoma mansoni in Haradenaba and Dertoramis kebeles in Bedeno district, eastern Ethiopia
Authors: Mohammed Jemal , Weldegebreal Fitsum , Teklemariam Zelalem , Mitiku Habtamu
Published: July 2018

Background:

Schistosoma mansoni is a major public health problem. Different studies reported unidentified sites in Ethiopia with variable prevalence and intensity, but there is no report from this study area.

Objective:

To assess the clinico-epidemiology, malacology, risk factors, and community awareness of S. mansoni in Haradenaba and Dertoramis kebeles in the Bedeno district, eastern Ethiopia.

Methods:

A cross-sectional study was conducted among 1011 study participants in 413 systematically selected households from Haradenaba and Dertoramis kebeles from 30 June 2016 to 30 July 2017. Data were collected by using pretested, structured questionnaires, clinical examinations, and stool examinations. Stool samples were processed by the Kato-Katz method and examined microscopically. Snails were collected by scooping from water contact points. Data were analyzed using SPSS, version 16 statistical software.

Result:

The overall prevalence of S. mansoni was 35.7%. Heavy-intensity infection was detected in 8.9% of the study participants. Results included: participants who were unaware about the possible source of infection (adjusted odds ratio: 2.95; 95% confidence interval: 1.25, 7.95), modes of transmission (adjusted odds ratio: 5.51; 95% confidence interval: 3.52, 12.51), prevention (adjusted odds ratio: 4.01; 95% confidence interval: 2.00, 8.75) about schistosomiasis/bilharziasis were more likely infected with S. mansoni than those who were aware. Participants who swim or bathe in the river were more likely infected with S. mansoni than those who do not (adjusted odds ratio: 6.41; 95% confidence interval: 3.15, 11.25). Biomphalaria pfeifferi snails were collected from all water bodies in Haradenaba and Dertoramis, but they did not shed schistosome cercaria in the laboratory.

Conclusion:

S. mansoni infection is found in high magnitude in these study areas, despite not being previously reported. A majority of the study participants had low awareness about the source of infection, mode of transmission, and prevention methods of schistosomiasis. Efforts should be made to improve community awareness about transmission and prevention of schistosomiasis.
Surgical site infection after primary total knee arthroplasty is associated with a longer duration of surgery
Authors: Teo Bryon Jun Xiong , Yeo William , Chong Hwei-Chi , Tan Andrew Hwee Chye
Published: July 2018

Purpose:

Surgical site infection (SSI) is a serious complication following total knee arthroplasty (TKA) leading to considerable morbidity. The incidence is reported to be up to 2%. Risk factors continue to be an area of intense debate. Our study aims to report the incidence of SSI and identify possible risk factors in our patients undergoing TKA.

Methods:

Prospectively collected data for 905 patients who underwent elective unilateral TKA by a single surgeon from February 2004 to July 2014 were reviewed. Patient demographics and relevant co-morbidities such as diabetes and heart disease were analysed. The presence of superficial wound infections and/or prosthetic joint infections was included.

Results:

The overall infection rate was 1.10% (10 of 905 patients). Six patients (0.66%) were diagnosed with superficial infections and four with PJI (0.44%). The mean operative duration for TKA with SSI was significantly longer at 90.5 ± 28.2 min, compared to 72.2 ± 20.3 min in TKA without SSI ( p = 0.03). All superficial infections occurred within the first month post-surgery and were self-limiting with oral antibiotics. The four patients with PJI required repeated procedures following TKA, including debridement, implant removal and/or revision arthroplasty. None of the 10 patients had a history of diabetes. There were no significant differences in demographics and co-morbidities between those who developed infection after TKA and those who did not.

Conclusion:

An overwhelming majority had good outcomes with only four deep infections resulting in revision surgery. We report that the risk of infection in TKA was significantly associated with a longer operative duration.
Does My Patient With Shoulder Pain Have a Rotator Cuff Tear? A Predictive Model From the ROW Cohort
Authors: Jain Nitin B. , Fan Run , Higgins Laurence D. , Kuhn John E. , Ayers Gregory D.
Published: July 2018

Background:

Rotator cuff tears are the leading cause of shoulder pain and disability. However, the diagnosis of a rotator cuff tear based on patient characteristics, symptoms, and physical examination findings remains a challenge because of a lack of data. Moreover, data on the predictive ability of a combination of these characteristics and tests are not available from a large cohort of patients. Consequently, clinicians rely on expensive imaging, such as magnetic resonance imaging (MRI), to make a diagnosis.

Purpose:

To model patient characteristics, symptoms, and physical examination findings that predict a rotator cuff tear. We present a nomogram based on our predictive model that can be used in patients with shoulder pain to determine the probability of the diagnosis of a rotator cuff tear without the need for imaging.

Study Design:

Cohort study (diagnosis); Level of evidence, 2.

Methods:

We recruited patients from outpatient clinics who were ≥45 years of age and who had shoulder pain of at least 4 weeks’ duration. A rotator cuff tear was diagnosed based on expert clinical impression and the presence/absence of a tear on a blinded review of MRI. Ultimately, 301 patients were included in the analysis.

Results:

A total of 123 patients (41%) had rotator cuff tears, and 178 patients (59%) did not. The predictors of the diagnosis of a rotator cuff tear included external rotation strength ratio of the affected versus unaffected shoulder (odds ratio [OR], 1.20 [95% CI, 1.08-1.34]), male sex (OR, 1.98 [95% CI, 1.10-3.56]), positive lift-off test result (OR, 4.33 [95% CI, 1.46-12.86]), and positive Jobe test result (OR, 9.19 [95% CI, 4.69-17.99]). A nomogram based on these predictor variables was plotted.

Conclusion:

Presented is a model that can accurately predict the diagnosis of a rotator cuff tear with satisfactory discrimination and calibration based on 4 variables: sex, lift-off test, Jobe test, and external rotation strength ratio. Data from this study can be used to aid in the diagnosis of a rotator cuff tear in day-to-day clinical practice in outpatient settings without the need for expensive imaging such as MRI.
Creating a comprehensive, unit-based approach to detecting and preventing harm in the neonatal intensive care unit
Authors: Sedlock Emily W , Ottosen Madelene , Nether Klaus , Sittig Dean F. , Etchegaray Jason M , Tomoaia-Cotisel Andrada , Francis Nicole , Yager Lauren , Schafer Leslie , Wilkinson Rebekah , Khan Amir , Arnold Cody , Davidson Allison , Thomas Eric J
Published: July 2018

Background

Error detection and analysis alone cannot create or sustain a culture of safe, high-quality, compassionate care for patients. Some experts have endorsed a unit-based approach to improving quality, but there are few examples and those rarely focus on reducing all preventable harms and engaging frontline clinicians, patients, and families. Approach: We implemented a unit-based approach comprising seven building blocks for creating a comprehensive approach to detect and prevent harm at the unit level within a hospital: (1) unit quality council and stakeholder buy-in, (2) parent engagement and advisory council, (3) frontline clinician and parent quality improvement training, (4) measurement of organizational contextual factors, (5) electronic health record trigger development and synthesis of harm measures, (6) subcommittees to review harm, and (7) quality improvement teams. Challenges and Lessons Learned: Challenges include conceptualizing triggers for a unit unfamiliar with this methodology, establishing unit resources for collecting and analyzing data, and creating processes to integrate parents in unit quality efforts. The seven essential building blocks helped overcome these challenges and could be adopted by other healthcare organizations.

Conclusion

These building blocks create a generalizable foundation for establishing a unit-based approach to detecting and preventing harm.
The rise of apoptosis: targeting apoptosis in hematologic malignancies
Authors: Valentin Rebecca , Grabow Stephanie , Davids Matthew S.
Published: July 2018

Dysregulation of the B-cell leukemia/lymphoma-2 (BCL-2) family of proteins of the intrinsic apoptotic pathway is fundamental to the pathophysiology of many hematologic malignancies. The BCL-2 family consists of regulatory proteins that either induce apoptosis (proapoptotic) or inhibit it (prosurvival). BCL-2, myeloid cell leukemia-1, and B-cell lymphoma–extra large are prosurvival proteins that are prime targets for anticancer therapy, and molecules targeting each are in various stages of preclinical and clinical development. The US Food and Drug Administration (FDA)-approved BCL-2 inhibitor venetoclax was first proven to be highly effective in chronic lymphocytic leukemia and some B-cell non-Hodgkin lymphoma subtypes. Subsequently, venetoclax was found to be active clinically against a diverse array of hematologic malignancies including multiple myeloma, acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, and others. Here, we give a brief introduction to BCL-2 family biology and the mechanism of action of BCL-2 Homology 3 (BH3) mimetics, and provide an overview of the clinical data for therapeutically targeting prosurvival proteins in hematologic malignancies, with a focus on BCL-2 inhibition. To prioritize novel agent combinations and predict responders, we discuss the utility of functional assays such as BH3 profiling. Finally, we provide a perspective on how therapies targeting BCL-2 family proteins may be optimally implemented into future therapeutic regimens for hematologic malignancies.
Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications
Authors: Fermand Jean-Paul , Bridoux Frank , Dispenzieri Angela , Jaccard Arnaud , Kyle Robert A. , Leung Nelson , Merlini Giampaolo
Published: July 2018

Monoclonal gammopathy is a common condition, particularly in the elderly. It can indicate symptomatic multiple myeloma or another overt malignant lymphoid disorder requiring immediate chemotherapy. More frequently, it results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only, defining a monoclonal gammopathy of unknown significance (MGUS). Sometimes, although quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone–related disorders, we propose to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti–B-cell/plasma cell agents, which should aim at rapidly producing the best hematological response.
Outcomes of Chemotherapy for Microsatellite Instable–High Metastatic Colorectal Cancers
Authors: Shulman Katerina , Barnett-Griness Ofra , Friedman Vered , Greenson Joel K. , Gruber Stephen B. , Lejbkowicz Flavio , Rennert Gad
Published: July 2018

Purpose

Microsatellite instable-high (MSI-H) colorectal cancers (CRCs) are known to carry better survival in the local disease stage even without treatment. The influence of types of treatment on survival of MSI-H metastatic CRCs (mCRCs) is still unclear and is evaluated in this study.

Materials and Methods

Patients with MSI-H mCRC treated with first-line chemotherapy, with or without bevacizumab, identified in the Israeli population-based Molecular Epidemiology of Colorectal Cancer (MECC) study, were diagnosed between 1998 and 2013 and followed up until May 2017; MSI status was determined by comparing 10 markers in tumor and normal tissue. Dates of metastases and death and treatment details were extracted from oncology records.

Results

Among 590 patients treated for mCRC, 106 (18%) had MSI-H tumors. Patients with MSI-H had a median overall survival (OS, from start of first-line treatment) of 1.6 years. The presence of a somatic B-Raf proto-oncogene ( BRAF) mutation was a significant adverse prognostic factor in the MSI-H group (hazard ratio [HR], 1.8; 95% CI, 1.1 to 3.0; P = .026). MSI-H tumors without BRAF mutation (n = 87) had similar OS benefit from fluorouracil (FU) only as from any combination protocols (HR, 0.93; P = .78), whereas microsatellite-stable (MSS) tumors without BRAF mutation (n = 456) showed improved OS over FU-only regimens when combination chemotherapy with or without bevacizumab was used (HR, 0.58; P < .01; P value for interaction = .07). Patients with MSI-H/BRAF wild type (WT) had survival advantage over patients with MSS disease (adjusted HR, 0.58; 95% CI, 0.35 to 0.98) when treated with FU-only protocols.

Conclusion

Clinical outcomes differ substantially between patients with MSS/BRAF-WT mCRC and MSI-H/BRAF-WT mCRC, with measurable differences between chemotherapy regimens. MSI-H mCRCs are a clinically distinct subset of colorectal cancers. Their current poor outcome suggests that new clinical trials are needed to identify therapeutic options, potentially taking advantage of the new developments in the field of immunotherapy.
Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe
Authors: Weems Peyton W , Coolen Lique M , Hileman Stanley M , Hardy Steven , McCosh Rick B , Goodman Robert L , Lehman Michael N
Published: July 2018

A subpopulation of neurons located within the arcuate nucleus, colocalizing kisspeptin, neurokinin B, and dynorphin (Dyn; termed KNDy neurons), represents key mediators of pulsatile GnRH secretion. The KNDy model of GnRH pulse generation proposes that Dyn terminates each pulse. However, it is unknown where and when during a pulse that Dyn is released to inhibit GnRH secretion. Dyn acts via the κ opioid receptor (KOR), and KOR is present in KNDy and GnRH neurons in sheep. KOR, similar to other G protein–coupled receptors, are internalized after exposure to ligand, and thus internalization can be used as a marker of endogenous Dyn release. Thus, we hypothesized that KOR will be internalized at pulse termination in both KNDy and GnRH neurons. To test this hypothesis, GnRH pulses were induced in gonad-intact anestrous ewes by injection of neurokinin B (NKB) into the third ventricle and animals were euthanized at times of either pulse onset or termination. NKB injections produced increased internalization of KOR within KNDy neurons during both pulse onset and termination. In contrast, KOR internalization into GnRH neurons was seen only during pulse termination, and only in GnRH neurons within the mediobasal hypothalamus (MBH). Overall, our results indicate that Dyn is released onto KNDy cells at the time of pulse onset, and continues to be released during the duration of the pulse. In contrast, Dyn is released onto MBH GnRH neurons only at pulse termination and thus actions of Dyn upon KNDy and GnRH cell bodies may be critical for pulse termination.
First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis
Authors: Philips Elise M , Kahn Linda G , Jaddoe Vincent W V , Shao Yongzhao , Asimakopoulos Alexandros G , Kannan Kurunthachalam , Steegers Eric A P , Trasande Leonardo
Published: July 2018

Background

Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP).

Methods

Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested.

Results

In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites.

Conclusions

We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.
Membrane fluctuations and acidosis regulate cooperative binding of ‘marker of self’ protein CD47 with the macrophage checkpoint receptor SIRPα
Authors: Steinkühler Jan , Różycki Bartosz , Alvey Cory , Lipowsky Reinhard , Weikl Thomas R. , Dimova Rumiana , Discher Dennis E.
Published: July 2018

Cell-cell interactions that result from membrane proteins binding weakly in trans can cause accumulations in cis that suggest cooperativity and thereby an acute sensitivity to environmental factors. The ubiquitous ‘marker of self’ protein CD47 binds weakly to SIRPα on macrophages, which leads to accumulation of SIRPα (also known as SHPS-1, CD172A and SIRPA) at phagocytic synapses and ultimately to inhibition of engulfment of ‘self’ cells – including cancer cells. We reconstituted this macrophage checkpoint with GFP-tagged CD47 on giant vesicles generated from plasma membranes and then imaged vesicles adhering to SIRPα immobilized on a surface. CD47 diffusion is impeded near the surface, and the binding-unbinding events reveal cooperative interactions as a concentration-dependent two-dimensional affinity. Membrane fluctuations out-of-plane link cooperativity to membrane flexibility with suppressed fluctuations in the vicinity of bound complexes. Slight acidity (pH 6) stiffens membranes, diminishes cooperative interactions and also reduces ‘self’ signaling of cancer cells in phagocytosis. Sensitivity of cell-cell interactions to microenvironmental factors – such as the acidity of tumors and other diseased or inflamed sites – can thus arise from the collective cooperative properties of flexible membranes.

This article has an associated First Person interview with the first author of the paper.
Chirping and asymmetric jamming avoidance responses in the electric fishDistocyclus conirostris
Authors: Petzold Jacquelyn M. , Alves-Gomes José A. , Smith G. Troy
Published: July 2018

Electrosensory systems of weakly electric fish must accommodate competing demands of sensing the environment (electrolocation) and receiving social information (electrocommunication). The jamming avoidance response (JAR) is a behavioral strategy thought to reduce electrosensory interference from conspecific signals close in frequency. We used playback experiments to characterize electric organ discharge frequency (EODf), chirping behavior, and the JAR of Distocyclus conirostris, a gregarious electric fish species. EODs of D. conirostris had low frequencies (∼80-200 Hz) that shifted in response to playback stimuli. Fish consistently lowered EODf in response to higher frequency stimuli but inconsistently raised or lowered EODf in response to lower frequency stimuli. This led to jamming avoidance or anti-jamming avoidance, respectively. We compare these behaviors to those of closely related electric fish (Eigenmannia and Sternopygus) and suggest that the JAR may have additional social functions and may not solely minimize the deleterious effects of jamming, as its name suggests.
Numerical Reconstruction of Traumatic Brain Injury in Skiing and Snowboarding
Authors: BAILLY NICOLAS , LLARI MAXIME , DONNADIEU THIERRY , MASSON CATHERINE , ARNOUX PIERRE-JEAN
Published: July 2018

Purpose

Proper evaluation of ski helmet designs and safety standards should rely on head impact conditions involved in skiing and snowboarding head injuries. To study these impacts, main crash scenarios involving head injuries are numerically replicated.

Methods

Multibody models of skiers and snowboarders were developed to investigate five common crash scenarios involved in traumatic brain injury: forward and sideways skiing falls, snowboarding backward falls, collisions between users and collisions with obstacles. For each scenario, the influence of crash conditions on head impact (location, speed, linear and rotational accelerations) and risk of injury are evaluated. Crash conditions were initial velocity, user height, position and approach angle, slope steepness, obstacles, and snow stiffness.

Results

One thousand one hundred forty-nine crashes were simulated and three significant levels of impact conditions were discriminated over the investigated crash scenarios: 1) the smallest normal-to-slope impact velocities (6 km·h−1; 22 km·h−1) and peak linear accelerations (42g; 75g) were obtained during forward and sideways skiing falls; 2) snowboarding backward falls and collisions between users were associated with high normal-to-surface impact velocities (26 km·h−1; 32 km·h−1) and head accelerations (80g; 149g) above one published threshold for mild traumatic brain injury but below the pass/fail criteria of helmet standard tests; 3) collisions with obstacles were associated with high normal-to-surface impact velocities (19 km·h−1; 35 km·h−1) and the highest head accelerations (626g; 1885g).

Conclusions

Current impact conditions of helmet standard evaluations consistently replicate collisions with obstacles, but need to be revised to better reflect other significant crash scenarios leading to traumatic brain injury.
A Dual-Accelerometer System for Classifying Physical Activity in Children and Adults
Authors: STEWART TOM , NARAYANAN ANANTHA , HEDAYATRAD LEILA , NEVILLE JONATHON , MACKAY LISA , DUNCAN SCOTT
Published: July 2018

Introduction

Accurately monitoring 24-h movement behaviors is a vital step for progressing the time-use epidemiology field. Past accelerometer-based measurement protocols are either hindered by lack of wear time compliance, or the inability to accurately discern activities and postures. Recent work has indicated that skin-attached dual-accelerometers exhibit excellent 24-h uninterrupted wear time compliance. This study extends this work by validating this system for classifying various physical activities and sedentary behaviors in children and adults.

Methods

Seventy-five participants (42 children) were equipped with two Axivity AX3 accelerometers; one attached to their thigh, and one to their lower back. Ten activity trials (e.g., sitting, standing, lying, walking, running) were performed while under direct observation in a lab setting. Various time- and frequency-domain features were computed from raw accelerometer data, which were then used to train a random forest machine learning classifier. Model performance was evaluated using leave-one-out cross-validation. The efficacy of the dual-sensor protocol (relative to single sensors) was evaluated by repeating the modeling process with each sensor individually.

Results

Machine learning models were able to differentiate between six distinct activity classes with exceptionally high accuracy in both adults (99.1%) and children (97.3%). When a single thigh or back accelerometer was used, there was a pronounced drop in accuracy for nonambulatory activities (up to a 26.4% decline). When examining the features used for model training, those that took the orientation of both sensors into account concurrently were more important predictors.

Conclusions

When previous wear time compliance results are taken together with our findings, it represents a promising step forward for monitoring and understanding 24-h time-use behaviors. The next step will be to examine the generalizability of these findings in a free-living setting.
Nano LC-MS using capillary columns enables accurate quantification of modified ribonucleosides at low femtomol levels
Authors: Sarin L. Peter , Kienast Sandra D. , Leufken Johannes , Ross Robert L. , Dziergowska Agnieszka , Debiec Katarzyna , Sochacka Elzbieta , Limbach Patrick A. , Fufezan Christian , Drexler Hannes C.A. , Leidel Sebastian A.
Published: July 2018

Post-transcriptional chemical modifications of (t)RNA molecules are crucial in fundamental biological processes, such as translation. Despite their biological importance and accumulating evidence linking them to various human diseases, technical challenges have limited their detection and accurate quantification. Here, we present a sensitive capillary nanoflow liquid chromatography mass spectrometry (nLC-MS) pipeline for quantitative high-resolution analysis of ribonucleoside modifications from complex biological samples. We evaluated two porous graphitic carbon (PGC) materials and one end-capped C18 reference material as stationary phases for reversed-phase separation. We found that these matrices have complementing retention and separation characteristics, including the capability to separate structural isomers. PGC and C18 matrices yielded excellent signal-to-noise ratios in nLC-MS while differing in the separation capability and sensitivity for various nucleosides. This emphasizes the need for tailored LC-MS setups for optimally detecting as many nucleoside modifications as possible. Detection ranges spanning up to six orders of magnitude enable the analysis of individual ribonucleosides down to femtomol concentrations. Furthermore, normalizing the obtained signal intensities to a stable isotope labeled spike-in enabled direct comparison of ribonucleoside levels between different samples. In conclusion, capillary columns coupled to nLC-MS constitute a powerful and sensitive tool for quantitative analysis of modified ribonucleosides in complex biological samples. This setup will be invaluable for further unraveling the intriguing and multifaceted biological roles of RNA modifications.
Increasing the length of poly-pyrimidine bulges broadens RNA conformational ensembles with minimal impact on stacking energetics
Authors: Merriman Dawn K. , Yuan Jiayi , Shi Honglue , Majumdar Ananya , Herschlag Daniel , Al-Hashimi Hashim M.
Published: July 2018

Helical elements separated by bulges frequently undergo transitions between unstacked and coaxially stacked conformations during the folding and function of noncoding RNAs. Here, we examine the dynamic properties of poly-pyrimidine bulges of varying length (n = 1–4, 7) across a range of Mg2+ concentrations using HIV-1 TAR RNA as a model system and solution NMR spectroscopy. In the absence of Mg2+, helices linked by bulges with n ≥ 3 residues adopt predominantly unstacked conformations (stacked population <15%), whereas one-bulge and two-bulge motifs adopt predominantly stacked conformations (stacked population >74%). In the presence of 3 mM Mg2+, the helices predominantly coaxially stack (stacked population >84%), regardless of bulge length, and the midpoint for the Mg2+-dependent stacking transition is within threefold regardless of bulge length. In the absence of Mg2+, the difference between free energy of interhelical coaxial stacking across the bulge variants is estimated to be ∼2.9 kcal/mol, based on an NMR chemical shift mapping with stacking being more energetically disfavored for the longer bulges. This difference decreases to ∼0.4 kcal/mol in the presence of Mg2+. NMR RDCs and resonance intensity data show increased dynamics in the stacked state with increasing bulge length in the presence of Mg2+. We propose that Mg2+ helps to neutralize the growing electrostatic repulsion in the stacked state with increasing bulge length thereby increasing the number of coaxial conformations that are sampled. Energetically compensated interhelical stacking dynamics may help to maximize the conformational adaptability of RNA and allow a wide range of conformations to be optimally stabilized by proteins and ligands.
DI-tector: defective interfering viral genomes’ detector for next-generation sequencing data
Authors: Beauclair Guillaume , Mura Marie , Combredet Chantal , Tangy Frédéric , Jouvenet Nolwenn , Komarova Anastassia V.
Published: July 2018

Defective interfering (DI) genomes, or defective viral genomes (DVGs), are truncated viral genomes generated during replication of most viruses, including live viral vaccines. Among these, “panhandle” or copy-back (cb) and “hairpin” or snap-back (sb) DI genomes are generated during RNA virus replication. 5′ cb/sb DI genomes are highly relevant for viral pathogenesis since they harbor immunostimulatory properties that increase virus recognition by the innate immune system of the host. We have developed DI-tector, a user-friendly and freely available program that identifies and characterizes cb/sb genomes from next-generation sequencing (NGS) data. DI-tector confirmed the presence of 5′ cb genomes in cells infected with measles virus (MV). DI-tector also identified a novel 5′ cb genome, as well as a variety of 3′ cb/sb genomes whose existence had not previously been detected by conventional approaches in MV-infected cells. The presence of these novel cb/sb genomes was confirmed by RT-qPCR and RT-PCR, validating the ability of DI-tector to reveal the landscape of DI genome population in infected cell samples. Performance assessment using different experimental and simulated data sets revealed the robust specificity and sensitivity of DI-tector. We propose DI-tector as a universal tool for the unbiased detection of DI viral genomes, including 5′ cb/sb DI genomes, in NGS data.
Two Centuries of Innovations and Stock Market Bubbles
Authors: Sorescu Alina , Sorescu Sorin M. , Armstrong Will J. , Devoldere Bart
Published: July 2018

The interplay between innovation and the stock market has been extensively studied by scholars across all business disciplines. However, one phenomenon remains understudied: the association between innovation and stock market bubbles. Bubbles—defined as rapid increases and subsequent declines in stock prices—have been primarily examined by economists who generally do not focus on individual characteristics of innovations or on the consequences of bubbles for their parent firms. We set out to fill this gap in our paper. Using a sample of 51 major innovations introduced between 1825 and 2000, we test for bubbles in the stock prices of parent firms subsequent to the commercialization of these innovations. We identify bubbles in 73% of the cases. The magnitude of these bubbles increases with the radicalness of innovations, with their potential to generate indirect network effects, and with their public visibility at the time of commercialization. Moreover, we find that parent firms typically raise new equity capital during bubble periods and that the amount of equity raised is proportional to the magnitude of the bubble. Finally, we show that the buy-and-hold abnormal returns of parent firms are significantly positive between the beginning and the end of the bubble, suggesting that these innovations add value to their firm and to the economy, in spite of the bubble. Our findings have important implications for managers interested in commercializing innovations and for policy makers concerned with the stability of the financial system.

Data and the online appendix are available at https://doi.org/10.1287/mksc.2018.1095 .
Paradise of Novelty—Or Loss of Human Capital? Exploring New Fields and Inventive Output
Authors: Arts Sam , Fleming Lee
Published: July 2018

Does a person become more or less creative when exploring a new field? Exploring new fields exposes a person to new knowledge that might increase the novelty of inventive output; at the same time, exploration means a lack of prior expertise and a learning challenge that might harm the value of that output. Using new combinations as a measure of novelty and citations as a measure of value, we demonstrate correlations between exploring new fields and increased novelty—but decreased value—in an inventor–firm fixed effects panel. The negative effect of exploring new fields on value is muted when the novice collaborates with experts or uses the scientific literature in the new field. We find consistent results using an unintended change in noncompete labor law as an exogenous influence on exploring new fields. The research illustrates two opposite influences of exploration on creative output and suggests how inventors can reduce the downside of entering a new field.

The online appendix is available at https://doi.org/10.1287/orsc.2018.1216 .
As Conferências Nacionais de Saúde e a política de saúde mental para a infância
Authors: Cabral Clariana Morais Tinôco , Francischini Rosângela
Published: July 2018

As políticas nacionais de saúde mental para a infância no Brasil constituem-se em uma tessitura complexa, ainda pouco explorada enquanto lócus de investigação, reflexão e crítica. Desta feita, compreender o percurso histórico pelo qual caminhou a saúde mental para a infância e juventude nesse país torna-se, também neste trabalho, um desafio a ser assumido. As Conferências Nacionais de Saúde (CNS) são tomadas como base referencial no presente trabalho, em virtude de seu pioneirismo, ao tornar as políticas brasileiras em saúde ações sistematizadas e organizadas em favor da efetivação de uma república democrática. A partir da análise dos relatórios produzidos com a realização das 14 CNS, pôde-se vislumbrar um panorama histórico mais fiel com relação à lógica proposta para atendimento das demandas em saúde mental infantil, ou o vácuo existente quanto à problematização e, consequentemente, à efetivação de ações que contemplem o seu seguimento.
O impacto da obra de J. B. Watson na psicologia norte-americana: Alguns parâmetros de comparação
Authors: Saraiva Fernando Tavares , Carvalho Neto Marcus Bentes de , Araujo Saulo De Freitas
Published: July 2018

O impacto da obra de J. B. Watson tem sido explorado na historiografia da psicologia. Neste âmbito, destacam-se estudos que utilizam como método a análise bibliométrica. Tais pesquisas, no entanto, não utilizam parâmetros comparativos que possam indicar de forma mais precisa o grau de impacto daquela obra. O presente estudo busca preencher tal lacuna por meio de uma análise bibliométrica comparativa das referências às obras de Watson e outros três relevantes psicólogos do período: Edward B. Titchener, Edward L. Thorndike e William James. A pesquisa foi realizada em cinco importantes periódicos norte-americanos da área, entre os anos 1903 e 1923 – uma década antes e uma década após a publicação do Manifesto Behaviorista. Os resultados permitem concluir que, embora não possa ser tomada propriamente como um marco revolucionário, a obra de Watson teve, na década posterior à publicação do Manifesto Behaviorista (1914-1923), um impacto próximo ao de Titchener e maior do que o de Thorndike, ainda que distante da influência exercida por James.
UM DEBATE SOBRE A QUESTÃO DA DIFERENÇA NAS POLÍTICAS DE CURRÍCULO
Authors: E Souza Alexandre Augusto
Published: July 2018

Resumo: As políticas de currículo são o tema deste artigo e o debate proposto trata a questão da diferença nas políticas curriculares. Busca-se compreender como é interpretada a diferença nas políticas de currículo, por meio da apreensão dos conceitos sobre política, currículo e diferença, bem como suas possíveis articulações. A pesquisa bibliográfica foi adotada como caminho de investigação e destacam-se as produções recentes sobre política curricular e a diferença, de Elizabeth Macedo e Alice Lopes, numa perspectiva pós-fundacional. Na perspectiva pós-fundacional compreende-se as políticas enquanto disputas por significação e a diferença é conceitualmente defendida como indecidível e imprevisível. Constata-se, com base nos estudos sobre políticas de currículo, a produção de inúmeras exclusões, o desejo de localizar e controlar o outro, o diferente.Palavras-chave: Currículo. Políticas de currículo. Diferença.Abstract: Curriculum policies are the theme of this article and the proposed debate addresses the issue of difference in curricular policies. It seeks to understand how the difference in curriculum policies is interpreted through the apprehension of concepts about politics, curriculum and difference, as well as their possible articulations. The bibliographical research was adopted as a way of investigation and the recent productions on curriculum policy and the difference, of Elizabeth Macedo and Alice Lopes, in post-foundational perspective. In the post-foundational perspective, understand the policies while disputes over meaning and the difference is conceptualized and defendeds undecidable and unpredictable. Notes, on the basis of studies on curriculum policies, the production of numerous exclusions, the desire to locate and control the other, the different.Keywords: Curriculum. Curriculum policies. Difference.
RHEUMATOID ARTHRITIS: THE PROBLEMS OF REMISSION AND THERAPY RESISTANCE
Authors: Nasonov E. L. , Olyunin Yu. A. , Lila A. M.
Published: July 2018

Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic visceral organ damage that results in early disability and shorter patient survival. Despite RA treatment advances associated with the design of novel drugs and the improvement of treatment strategies to achieve remission in many patients, there are still many theoretical and clinical problems concerning both the definition of the concept of remission, its characteristics and types and approaches to the optimum policy of symptomatic and pathogenetic drug therapy at different stages of the disease, the use of which will be able to rapidly induce and maintain remission in the long-term. Further investigations are needed to study the nature of heterogeneity of pathogenetic mechanisms of RA and approaches to early diagnosis, to improve methods for monitoring disease activity and biomarkers for the efficiency of and resistance to therapy and, finally, to develop differentiation therapy, including those related to a search for new therapeutic targets.
ACCORDING TO THE MATERIALS OF THE 2015/2016 NEW EUROPEAN LEAGUE AGAINST RHEUMATISM (EULAR) GUIDELINES FOR REDUCING CARDIOVASCULAR RISK IN PATIENTS WITH INFLAMMATORY ARTHRITIS: GENERAL CHARACTERIZATION AND DISCUSSION PROBLEMS
Authors: Popkova T. V. , Novikova D. S.
Published: July 2018

According to the materials of the 2015/2016 new European League Against Rheumatism (EULAR) guidelines for reducing cardiovascular risk in patients with inflammatory arthritis. The authors identify three main principles of prevention of cardiovascular diseases in rheumatoid arthritis and other chronic inflammatory arthritis and provide a general characterization of the guidelines, by reviewing the discussion problems.
EXTRA-ARTICULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS
Authors: Muravyev Yu. V.
Published: July 2018

Rheumatoid arthritis (RA) is an immune inflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic damage to the viscera, and leads to early disability and reduced survival in patients. For its diagnosis, it is currently recommended to use the 2010 ACR/EULAR classification criteria for RA, which should be applied in clinical trials to identify at least one swollen joint, i.e. the presence of arthritis; therefore, the problem of extra-articular manifestations of RA is apparent to stay in the background.
VACCINATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS AND PROSPECTS
Authors: Belov B. S. , Solovyev S. K. , Tarasova G. M. , Aseeva E. A.
Published: July 2018

The importance of comorbid infections in rheumatology has increased substantially in recent years, particularly in connection with the introduction of biological agents into clinical practice. One of the ways to solve this problem is to study and actively use vaccines. This review deals with the issues related to the use of vaccines against various infections in patients with systemic lupus erythematosus. It discusses the safety and immunogenicity of vaccination, including the use of adjuvant vaccines. Cardinal directions for future investigations of the problem are denoted.
DEFINITION OF THE TERM «RHEUMATOLOGY»: DO WE NEED THIS AND HOW DO THE EULAR AND THE ACR LOOK AT THIS?
Authors: Erdes Sh. F.
Published: July 2018

The paper discusses the article «Common language description of the term rheumatic and musculoskeletal diseases (RMDs) for use in communication with the lay public, healthcare providers and other stakeholders endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR)» that appeared in the on-line first journal Annals of the Rheumatic Diseases in March 2018. It is shown that, on the one hand, the development of the definition is positive, but, on the other, blurs the verges of rheumatology due to the introduction of nosological entities that are absolutely unrelated to our profession.
A group-theoretical approach for nonlinear Schrödinger equations
Authors: Molica Bisci Giovanni
Published: July 2018

The purpose of this paper is to study the existence of weak solutions for some classes of
Schrödinger equations defined on the Euclidean space

ℝ
d

{\mathbb{R}^{d}}

(

d
≥
3

{d\geq 3}

). These equations have a
variational structure and, thanks to this, we are able to find a non-trivial weak solution for them
by using the Palais principle of symmetric criticality and a group-theoretical approach used on a suitable closed subgroup of the orthogonal group

O
⁢

(
d
)

{O(d)}

. In addition, if the nonlinear term is odd, and

d
>
3

{d>3}

, the existence of

(

-
1

)

d

+

[

d
-
3

2

]

{(-1)^{d}+[\frac{d-3}{2}]}

pairs of sign-changing solutions has been proved. To make the nonlinear setting work, a certain summability of the

L
∞

{L^{\infty}}

-positive and radially symmetric potential term W governing the Schrödinger equations is requested. A concrete example of an application is pointed out. Finally, we emphasize that the method adopted here should be applied for a wider class of energies largely studied in the current literature also in non-Euclidean setting as, for instance, concave-convex nonlinearities on Cartan–Hadamard manifolds with poles.
Design a Compact UWB Monopole Antenna with Triple Band-Notched Characteristics Using EBG Structures
Authors: Mouhouche F. , Azrar A. , Dehmas M. , Djafri K.
Published: July 2018

In this paper, a compact ultra-wideband (UWB) monopole antenna with triple band-notched characteristics is presented. These triple band rejections are produced by inserting the Complementary Co-directional Split-Ring Resonator (CC.SRR) on the radiating element for WiMAX/WLAN (3.4–3.95 GHz/5.35–5.9 GHz) and Electromagnetic Band Gap (EBG) structure in the vicinity of transmission line for X-band satellite communications (6.7–7.7 GHz). The proposed antenna with a total size of 18×20.9×1.63 mm3 has been constructed and tested. An equivalent RLC circuit model is proposed and investigated. The simulated and measured results show that the proposed antenna has an impedance bandwidth (VSWR<2) extanding from 3.05 GHz to 14 GHz with triple notched bands of [3.3–3.9 GHz], [5.25–5.86 GHz] and [6.7–7.7 GHz]. The triple band notched characteristics and the good radiation patterns make the proposed antenna a good candidate for the UWB applications.
Illegitimate or Legitimate Non-Tariff Measures
Authors: Marette Stéphan
Published: July 2018

This paper analyzes whether or not a standard reducing risks and influencing firms' entry is protectionist and can be interpreted as an illegitimate non-tariff measure (NTM). Domestic and foreign firms compete in selling products in the domestic market, in the presence of possible damages and endogenous sunk costs for reducing the risks of having these damages. A policymaker chooses a standard that is imposed on all firms, but may also impede their ability to enter the domestic market. Welfare can be improved with a legitimate NTM, particularly under relatively high levels of sunk costs and damages, justifying a reduction in the number of firms allowing a higher effort for curbing the expected damage. Protectionism related to an illegitimate NTM occurs when the standard maximizing domestic or foreign welfare is higher than the international standard, maximizing the world (or global) welfare inclusive of all profits and surpluses across countries. The characterization of protectionism is influenced by the domestic or foreign origin of firms, and by the nature of the expected damage incurred at either the production level or the consumption level. Configurations with expected damages related to consumption tend to exhibit more cases of protectionism compared to configurations with expected damages related to production.