bluuebunny/crossref_metadata_2025 huggingface dataset:
If You Build It, Will They Come? Exploring Narratives That Shape the Internet in Nepal
Authors: Pandey Shailesh B. , Regmi Nischal
Published: May 2020

Nepali information and communication technology (ICT) policies, informed by dominant international discourses on internet and ICT for development, have attributed a ‘self-evident’ positive impact to economic growth. Such a conception is inconclusive and hides the underlying socioeconomic inequalities and the barriers they oppose to universal connectivity ambitions. The self-evident discourse overlooks the importance of adjacent infrastructures like electricity, critical for efficient functioning of a ‘digital society’. History has shown Nepal’s eagerness to buy the irrational exuberance of the dot-com era. It also shows policy targets were not based on local evidence and experiences. While the question about when the next bubble will emerge and burst is debatable, the techno-deterministic arguments need to be checked in light of evidence. We offer insights from import trajectories since the drafting of the first IT policy. The proliferation of mobile phones is explored in light of data consumption (i.e., usage) and access during the deadly earthquake in 2015. The evidence clearly highlights the mismatch between connectivity ambitions and socioeconomic realities in a stratified information society. We contend that the self-evident visions of connectivity need to be checked empirically. We call for internet and ICT policies that have a nuanced conceptualisation of access and its gradation.
The Evolution and Testing of Aerial Lift Anti-Entrapment Safety Devices
Authors: Rasnic Russ , Beard Edward L. , Wehmeyer Steven
Published: May 2020

First introduced in the 1950’s [2], aerial lifts, also known as cherry pickers, aerial work platforms, and boom lifts, have enabled workers to perform tasks at elevated heights much easier. In many applications with overhead obstructions however, these lifts also present a severe risk to the users, often including fatality. The user can become entrapped due to unintentional involvement with overhead obstacles and be crushed between the lift and the obstacle. In this paper, we present the evolution of the common safety features and anti-entrapment devices that have been developed in response to the growing awareness of the prevalence of these injuries. After these devices are discussed, results are shown for experimental testing of potential crush mechanisms and representative forces. To test the crush force, load cells are attached to a stationary plate in front of a test dummy and forces are recorded to evaluate potential entrapment scenarios. Representative safety device designs are tested, which include mechanical, electrical, and audible features to stop and/or reverse the direction of movement to mitigate or prevent injury. All tests show that having an anti-entrapment device installed drastically reduces the risk to the user and likely prevents fatalities.
Influence of microalgae addition in formulation on colour, texture, and extrusion parameters of corn snacks
Authors: Uribe-Wandurraga Zaida Natalia , Igual Marta , García-Segovia Purificación , Martínez-Monzó Javier
Published: May 2020

Extrusion is a more and more popular technique for snack production using interesting raw ingredients, to produce snacks improving their nutritional value. The aim of this study was to obtain corn extrudates enriched with different concentration levels of Arthrospira platensis, Chlorella vulgaris, and Nannochloropsis gaditana biomass and to compare their expansion parameters and physicochemical properties with control corn extrudates. Expansion, physicochemical, and compositional parameters were analysed. Microalgae addition to formulations gave extruded snacks and provoked no major changes compared to control corn extrudate. Addition of microalgae in extrudates formulation implies a slight reduction of water absorption index, swelling index, bulk density, and hygroscopicity and a slight increase in water solubility index, expansion index, and porosity. Noticeable changes for the addition of microalgae changed the extruded snack from translucent to opaque and total colour difference values of were perceptible by human eye.
European real-world data about the use of a new delivery system containing a preservative-free multi-dose glaucoma treatment
Authors: Denis Philippe , Duch Susana , Chen Enping , Klyve Per , Skov Jesper , Puska Païvi , Erb Carl
Published: May 2020

Background

Glaucoma treatments are mostly presented in uni-dose or multi-dose format. A certain number of patients with visual acuity and dexterity problems may have problems in instilling eye drops.

Aim

To assess patient satisfaction and ease of use of a preservative-free glaucoma treatment (dorzolamide/timolol) in a new and innovative patented multi-dose delivery system.

Methods

Retrospective, international, multicentre, non-interventional study in 788 adult patients using a multi-dose delivery system for at least 28 days.

Results

Mean patient age was 68.1 ± 12.1 years. Mean duration of multi-dose delivery system use was 132.1 ± 125.1 days; 66.5% of the patients previously used multi-dose and 33.5% uni-dose delivery systems (n = 734); 78.3% of the patients were satisfied or very satisfied with the multi-dose delivery system. A significant majority (all p ≤ 0.045) of patients with a QuickDash® score between [0 to 25[ (66.4%, n = 211) and [50 to 75[ (81.8%, n = 11) rated multi-dose delivery system as easy or very easy to open and significantly more subjects in the [0 to 25[ (72%) score group rated multi-dose delivery system as being better or much better than their previous device (n = 211). Significantly (all p < 0.01) more subjects with available visual acuity results rated multi-dose delivery system as good, better or much better than their previous dispensing device.

Conclusion

The tested multi-dose delivery system was highly accepted. It is, therefore, suitable for glaucoma patients with decreased visual acuity and/or dexterity problems. Further studies may be necessary to assess the easiness of use of this easy-to-grip delivery system.
Novel Use of the Urchin® Heart Positioner for Repair of Pericardial Rupture in Cardiac Subluxation: Case Report and Review of Management
Authors: Sarkeshik Amir A. , Jamal Ala Z. , Rodriguez Victor M.
Published: May 2020

A 65-year-old man was involved in a multivehicle collision from which he sustained blunt polytrauma involving the abdomen and chest. Imaging of the chest revealed biventricular cardiac herniation into the left chest with an associated pneumopericardium. He underwent emergent surgical management with repositioning of the heart and repair of associated pericardial rupture. Exposure was facilitated with the novel use of an off-pump coronary surgery heart positioner. This report highlights the management of these rare blunt traumatic injuries in addition to using the Urchin® heart positioner for optimal exposure.
Two-Step Optimization to Develop a Transdermal Film Loaded With Dapoxetine Nanoparticles: A Promising Technique to Improve Drug Skin Permeation
Authors: Ahmed Tarek A. , Alay Asmaa M. S. , Okbazghi Solomon Z. , Alhakamy Nabil A.
Published: May 2020

Dapoxetine (DPX) is an orally administered drug for the treatment of premature ejaculation (PE). One of the challenges of administering DPX orally as a tablet is its poor bioavailability (ie, 42%) due to extensive first-pass metabolism. Thus, it is vital to develop a new formulation and mode of delivery to achieve the unmet needs of PE treatment. In this study, an optimized DPX polymeric nanoparticle (PNP) was developed and subsequently loaded into a transdermal film. The Box–Behnken design was utilized to optimize 3 formulation factors affecting the particle size and entrapment efficiency (EE) of chitosan (CS)-alginate (ALG) PNPs. A 3-level factorial design was used to study the effect of 2 variables affecting DPX cumulative percent released and percent elongation from transdermal films loaded with DPX-PNPs. Permeation parameters were calculated following ex vivo permeation study through rat skin. Transport of the PNPs across the skin layers was investigated using a fluorescence laser microscope. Results revealed that an optimized PNPs formulation was developed with a particle size 415.94 nm and EE 37.31%. Dapoxetine was successfully entrapped in the polymeric matrix. Chitosan and ALG interacted electrostatically with the studied cross-linking agents to form a polyelectrolyte complex. The ex vivo study illustrated a sustained release profile of DPX with enhanced skin permeation from the film loaded PNPs. Moreover, the PNPs was able to penetrate deeper into skin layers. Therefore, DPX transdermal film developed in this work could be considered as a successful drug delivery with better patient compliance for the treatment of PE.
Chronic Postoperative Pain After Hysterectomy for Endometrial Cancer: A Metabolic Profiling Study
Authors: Lunde Søren , Nguyen Hien TT , Petersen Kristian K , Arendt-Nielsen Lars , Krarup Henrik B , Søgaard-Andersen Erik
Published: May 2020

Introduction

One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low‐molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain.

Materials and Methods

The study was designed as a nested case–control study within a cohort of women treated for endometrial cancer with robot-assisted laparoscopic hysterectomy. Twenty-six women with chronic postoperative pain were matched on age and body mass index with fifty-two controls without chronic postoperative pain, and metabolic profiling of preoperatively drawn blood samples from a biobank was performed by means of nuclear magnetic resonance spectroscopy.

Results

Nineteen metabolites, including cholesterol, cholesteryl ester, linoleic acid, phospholipids, lipids, and triglycerides had statistically significant higher concentrations in a subgroup of patients who would develop chronic postoperative pain on a later stage compared to the group of patients who would not develop chronic postoperative pain ( p <  0.05). A sparse Partial Least Squares-Discriminant Analysis model explained 38.1% of the variance and had a predictive accuracy of 73.1%.

Conclusions

This explorative study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.
The Belt and Road Initiative and the Eurasian Economic Union: Exploring the “Greater Eurasian Partnership”
Authors: Shakhanova Gaziza , Garlick Jeremy
Published: May 2020

The Russian-led Eurasian Economic Union (EAEU) is a key partner in China’s Belt, and Road Initiative (BRI), since it comprises the majority of territories which the BRI’s overland route, the Silk Road Economic Belt, needs to traverse as it crosses Central Asia on the way to Europe. The goal of this article is to explore the BRI in the context of BRI–EAEU coordination. The first part of the analysis focusses on the ways the Eurasian Economic Commission delineates the “Greater Eurasian Partnership” and counterposes it against China and the BRI. Then, the article compares two sets of interpretations of the BRI and “Greater Eurasian Partnership” obtained from interviews with elites in Kazakhstan and Russia. The interviews indicate that the BRI has had a much more forceful impact on local elites than Russia’s idea of “Greater Eurasian Partnership.”
Interparty and Intraparty Factionalism in Cambodian Politics
Authors: Peou Sorpong
Published: May 2020

Cambodia’s hegemonic party system that emerged after the violent removal of First Prime Minister Norodom Ranariddh early in July 1997 has now given way to a one-party state, which still remains prone to tension and instability. The party system has become less factionalised and can be characterised as moving from high to medium factionalism. This development resulted from the growing domination of the Cambodian People’s Party (CPP) and the weakening of the opposition parties, such as National United Front for an Independent, Netural, Peaceful and Cooperative Cambodia, which splintered and become almost irrelevant in Cambodian politics. The Cambodian National Rescue Party (CNRP) emerged as the main opposition party after the 2013 election but was then banned from competing in the 2018 election. Although the CNRP remains united by its anti-CPP position, it is still fractured along political lines between two former opposition parties – the Sam Rainsy Party and the Human Rights Party. Historical institutionalism sheds some new light on the variation of political developments among political parties and within them, but does not supplant the fact that party leaders are rational to the extent that they select strategies in pursuit of their interests defined as power or security under specific institutional constraints or the lack thereof.
Novel 1,3-Benzodioxole From Marine-Derived Actinomycete in East Vietnam Sea
Authors: Phi Thi Dao , Doan Thi Mai Huong , Cao Duc Danh , Vu Thi Quyen , Nguyen Mai Anh , Le Thi Hong Minh , Tran Dang Thach , Chau Van Minh , Pham Van Cuong
Published: May 2020

Analysis of an antimicrobial extract from the culture broth of the marine-derived actinomycete Streptomyces sp. G261 led to the isolation of a new 1,3-benzodioxole derivative (1), together with 10 known compounds 2-11. The actinomycete strain G261 was isolated from sediment, collected at Cu Lao Cham, Quang Nam in Vietnam. The taxonomic identification of the strain G261 was achieved by analysis of 16SrRNA gene sequences. On the basis of morphological and phylogenetic evidence, the actinomycete strain G261 was assigned to the genus Streptomyces. The structures of the isolated compounds were established by their spectral data analysis, including mass spectrometry, 1-dimensional nuclear magnetic resonance (1D-NMR), and 2D-NMR. The structure of 1 was confirmed by comparison of the calculated with experimental 13C NMR data. Compound 1 exhibited antimicrobial activity against Enterococcus faecalis and Staphylococcus aureus with minimum inhibitory concentration values of 128 and 256 µg/mL, respectively. Whereas, compound 1 had a weak inhibition when tested against 4 cancer cell lines, KB, LU-1, HepG-2, and MCF-7.
Instagram use frequency is associated with problematic smartphone use, but not with depression and anxiety symptom severity
Authors: Rozgonjuk Dmitri , Pruunsild Patrik , Jürimäe Kadi , Schwarz Rosiine-Johanna , Aru Jaan
Published: May 2020

Studies have demonstrated that social media use, as well as problematic smartphone use (PSU), are associated with psychopathology variables, such as depression and anxiety. However, it has not been studied how Instagram use frequency is associated with depression, anxiety, and PSU. The aim of this study was to investigate whether Instagram use frequency is related to these psychopathology variables. Three hundred and five active Instagram users ( Mage = 23.61, SDage = 5.33; 82.2% female) comprised the effective sample in this study. They responded to an online survey that included questionnaires regarding their Instagram and smartphone use, as well as about experiencing depression and anxiety symptoms. We also retrieved objectively measured Instagram use data. The results showed that although Instagram use frequency, depression, and anxiety were associated with PSU in bivariate analysis, Instagram use frequency did not have indirect effects in the relations between psychopathology variables and PSU. Furthermore, while younger age and female sex predicted Instagram use frequency, these socio-demographic variables did not predict PSU. According to our findings Instagram use frequency contributes to PSU, but it is not related to depression and anxiety.
Synchronous squamous cell carcinoma and papillary thyroid carcinoma arising from the thyroglossal duct remnant: Case report and a review of the literature
Authors: Puccini Marco , Roffi Nicolò , Pucci Valentina , Fiacchini Giacomo , Ugolini Clara , Buccianti Piero
Published: May 2020

Squamous cell carcinoma and papillary thyroid carcinoma simultaneously spreading from the thyroglossal duct remnant (TGDR) is a very rare event. The recognition of this condition allows a correct management and treatment, offering the best chances of cure to the patient. We describe the case of a 42-year-old woman who noticed a right-sided lump in her neck. An ultrasound scan confirmed multiple clusters of enlarged lymph nodes on the right side associated to a pre-hyoidal solid nodule. The thyroid gland was normal. Fine-needle aspiration cytology on two nodes revealed distinct metastases from squamous cell carcinoma and from papillary thyroid carcinoma. A careful screening for other head and neck tumors was negative. She underwent a Sistrunk procedure, total thyroidectomy and right lateral lymphadenectomy with en bloc jugular vein resection. On histology, a 2 cm papillary and a small squamous cell carcinoma of the TGDR were documented, with nodal metastases from both primaries. We report the overall management strategy, treatment and outcome at 26-month follow-up, and a review of the literature.
Spontaneously ruptured hepatocellular carcinoma in Fontan-associated liver disease: A case report
Authors: Kubo Takahiro , Aihara Yosuke , Kawaratani Hideto , Namisaki Tadashi , Noguchi Ryuichi , Mitoro Akira , Yoshiji Hitoshi
Published: May 2020

The prognosis of congenital heart disease is dramatically improved by cardiac surgery. The Fontan procedure is the definitive palliative operation for patients with single-ventricle physiology. In parallel with the longer survival time achieved with the Fontan procedure, the incidence of Fontan-associated liver disease is increasing. A 40-year-old man who underwent Fontan procedures at the ages of 9 was referred to our hospital for further evaluation of multiple hepatic tumors. Enhanced computed tomography showed large hepatocellular carcinomas with portal thrombi (Vp3). Spontaneous hepatocellular carcinoma rupture occurred 2 weeks after the first visit to our hospital, and emergent transcatheter arterial embolization of the hepatic artery was performed. Three months later, the patient died of liver failure. Autopsy findings showed moderately differentiated hepatocellular carcinoma with a cirrhotic liver characterized by centrilobular fibrosis and sinusoidal dilation similar to that in Fontan-associated liver disease. We reported the first case of spontaneously ruptured hepatocellular carcinoma treated by emergent transcatheter arterial embolization in Fontan-associated liver disease. As the early diagnosis of liver cirrhosis and hepatocellular carcinoma results in better patients’ outcome, cardiologists and hepatologists should be aware of Fontan-associated liver disease and advise patients to have regular follow-up of the liver.
Streamlined haematuria pathway: Reduced waiting times and improved cost benefits
Authors: Wood Brielle E , Kim Jason , Donato Peter , Mostyn Jenna , McClintock Scott
Published: May 2020

Objectives:

Haematuria is a common urological complaint that carries a significant burden to our healthcare system. Due to the complex investigation algorithm for haematuria, incomplete referrals result in multiple appointments. We established the “streamlined haematuria pathway” (SHP) phone clinic, and this study evaluated the effect of SHP on waiting times, patient care and time to treatment.

Methods:

A retrospective analysis of all patients who were reviewed via our SHP was performed, including time to see and outcomes. The effects of implementing the SHP on our health system were assessed by analysing our referral waitlists and costings department.

Results:

On starting the SHP phone clinic there were 1031 referrals waiting longer than clinical recommended time frames, and of these 92 were identified as a patient with haematuria. The majority of patients were male sex (55%), had microscopic haematuria (63%), and the median age was 69 years. There were 12 (30%) patients who were waiting 100 days or more before the phone clinic was introduced. A total of 87% patients were discharged post-normal outcomes, 5% patients had stones and 8% patients were diagnosed with bladder malignancy.

Conclusions:

The SHP phone clinic is an effort to decrease morbidity and mortality by earlier diagnosis of urological malignancy.

Level of evidence:

3-b
Boosting Health Campaign Reach and Engagement Through Use of Social Media Influencers and Memes
Authors: Kostygina Ganna , Tran Hy , Binns Steven , Szczypka Glen , Emery Sherry , Vallone Donna , Hair Elizabeth
Published: May 2020

Public health organizations are increasingly turning to social media as a channel for health campaign dissemination, as these platforms can provide access to “hidden” or at-risk audiences such as populations of color and youth. However, few studies systematically assess the effects of such campaigns in a competitive communication environment characterized by an influx of sophisticated tobacco product marketing. The objective of the current study is to investigate how content and source features of Twitter messages about truth® campaigns influence their popularity, support, and reach. Keyword rules were used to collect tweets related to each of the six campaigns from the Twitter Firehose posted between August 2014 and June 2016. Data were analyzed using a combination of supervised and unsupervised machine learning, keyword algorithms, and human coding. Tweets were categorized by source type (direct or truth®-owned social influencer; non-influencer). Tweet content was coded and classified for valence and campaign references (branded vs. non-branded or organic content). Message reach was calculated by source type and message type. Keyword filters captured 308,216 tweets posted by 225,912 Twitter users. Findings revealed that campaigns that utilized social influencers as message sources generated more campaign-branded and sharable content (e.g., campaign hashtags) and greater volume of tweets per day and reach per day. Influential users posted fewer organic messages and more branded/sharable content, generating greater reach compared to non-influencers. Oppositional messages decreased over time. Harnessing cultural elements endemic to social media, such as popular content creators (influencers) and messages (memes), is a promising strategy for improving health campaign interest and engagement.
Acceptance of Traditional Chinese Medicine in the Neonatal Intensive Care Unit: A Launching Point
Authors: Johnson Rolfes Julie , Christensen Kimberly , Gershan Lynn A
Published: May 2020

Background

Because neonatology is a relatively new medical specialty, it is host to on-going, rapid adaptation and evolution of medical treatments and practices. This process has almost exclusively focused on Western, biomedical treatment modalities, without inclusion of potentially beneficial Traditional Chinese Medicine practices. It is unclear how receptive health-care providers in the neonatal intensive care unit (NICU) and families of NICU patients would be to the introduction of adapted Traditional Chinese Medicine treatments into the NICU environment.

Objective

To assess the potential for engagement of patients, families, and staff in the NICU with Traditional Chinese Medicine therapies and to provide targeted education and low-risk Traditional Chinese Medicine treatments to support the health and well-being of those 3 groups.

Methods

A feasibility pilot study including weekly walk-in Traditional Chinese Medicine sessions within the NICU for parents and staff, and neonatal patient consultations, both of which included hands-on therapies and education tailored to each participant's unique needs. Pre- and postsurveys were administered over 3 phases.

Results

Walk-in sessions were attended by 83 adults and participants reported benefits, with no ill effects. There were 5 neonatal consultations with staff expressing an interest in more. Several obstacles to accessing Traditional Chinese Medicine modalities were identified in pre-surveys and were addressed with education and preemptive modifications to the therapies offered.

Conclusion

Acceptance of Traditional Chinese Medicine modalities in the NICU opens the door to future studies implementing integrative health services into the NICU care model.
A Longitudinal Study Examining Dual Enrollment as a Strategy for Easing the Transition to College and Career for Emerging Adults
Authors: Henneberger Angela K. , Witzen Heath , Preston Alison M.
Published: May 2020

Successfully transitioning to adulthood requires a successful transition from high school into college or the workforce. Yet for many emerging adults, this transition is not successful, leading to disengagement from school and work. Dual enrollment, where high school students enroll in college coursework, may help to facilitate this important life transition. This study applied propensity score matching to statewide administrative data to investigate the effects of dual enrollment on college and early labor market outcomes. We found a significant effect of dual enrollment on 2-year and 4-year college enrollment, degree attainment, and early labor market earnings 6 years after high school, with stronger effects for students who are traditionally underrepresented (e.g., Black and Other race students and students eligible for free and reduced price meals). This study highlights the potential for targeting dual enrollment programs toward underrepresented students to improve the transition into college and the workforce for emerging adults.
Selective Fusion in Lenke 1 B/C: Before or After Menarche?
Authors: Davies Nestor Ricardo , Tello Carlos , Piantoni Lucas , Remondino Rodrigo , Galaretto Eduardo , Wilson Ida Alejandra Francheri , Rodriguez Victor Vasquez , Bersusky Ernesto , Noel Mariano
Published: May 2020

Study Design:

A retrospective, comparative study.

Objective:

To determine the radiological behavior of the lumbar curve in selective fusions in premenarchal girls with adolescent idiopathic scoliosis (Lenke 1 B/C).

Methods:

A retrospective, comparative study was conducted. Selective fusion was performed in 21 patients younger than 18 years. The patients were divided into 2 groups: group A, after menarche (n = 12) and group B, before menarche (n = 9). Angles (preoperative, and at 1 and 2 years postoperatively) of the fused thoracic curves and the corresponding lumbar curves were measured and compared. For statistical analysis, the t test was used with a significance level of P < .05.

Results:

Mean preoperative angle value of the proximal/main thoracic curve was 61° in group A and 57° in group B ( P = .44), and 21° and 20°, respectively, in the first year postoperatively ( P = .61). Mean preoperative angle value of the lumbar curve was 43° in group A and 42° in group B ( P = .87), while at 1 year after surgery, this curve was 19° in both groups ( P = 0.91), and at 2 years postoperatively, the curve was 16° in group A and 17° in group B ( P = .75).

Conclusions:

Over a 2-year follow-up, we did not find significant radiological differences in lumbar curves between patients who underwent surgery before and after menarche.
Does L5-S1 Anterior Lumbar Interbody Fusion Improve Sagittal Alignment or Fusion Rates in Long Segment Fusion for Adult Spinal Deformity?
Authors: Meyers Andrew J. , Wick Joseph B. , Rodnoi Pope , Khan Ahsan , Klineberg Eric O.
Published: May 2020

Study Design:

Retrospective cohort study.

Objectives:

To assess whether the addition of L5-S1 anterior lumbar interbody fusion (ALIF) improves global sagittal alignment and fusion rates in patients undergoing multilevel spinal deformity surgery.

Methods:

Two-year radiographic outcomes, including lumbar lordosis, pelvic incidence, pelvic tilt, and T1 pelvic angle; hardware complications; and nonunion/pseudarthrosis rates were compared between patients who underwent lumbosacral fusion at 4 or more vertebral levels with and without L5-S1 ALIF between November 2003 and September 2016.

Results:

A total of 51 patients who underwent fusion involving a mean of 11.1 levels with minimum 2-year postoperative radiographic follow-up data were included. Patients who underwent L5-S1 ALIF did not have significant improvement in global sagittal alignment parameters and demonstrated a trend toward a higher rate of nonunion and hardware failure.

Conclusions:

L5-S1 ALIF did not confer significant benefit in terms of global sagittal alignment and fusion rates in patients undergoing multilevel lumbosacral fusion. Given these results and that L5-S1 ALIF is associated with increased surgical morbidity, surgeons should be judicious in including L5-S1 ALIF in large multilevel constructs.
Evidence-Based Practice in Mission: A Method for Establishing Best Practices and Achieving Desired Goals
Authors: Morgan J. Rupert
Published: May 2020

Decision making and strategy in missions can be elusive tasks. The presence of experts and careful planning may not assure the establishment of best practices. The purpose of this article is to introduce evidence-based practice (EBP) as a proven method for establishing best practices in the mission enterprise. I will provide (1) a definition of EBP, (2) the process for establishing an EBP, (3) the value of EBP and its contribution to the mission enterprise and the fulfillment of mission goals, and (4) the problem of bias and barriers, which challenges the implementation of EBP.
A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle
Authors: Chen Xuejie , Li Caihong , Jin Da-Yun , Ingram Brian , Hao Zhenyu , Bai Xue , Stafford Darrel W. , Hu Keping , Tie Jian-Ke
Published: May 2020

Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K–dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.
Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results
Authors: Gardin Claude , Pautas Cécile , Fournier Elise , Itzykson Raphaël , Lemasle Emilie , Bourhis Jean-Henri , Adès Lionel , Marolleau Jean-Pierre , Malfuson Jean-Valère , Gastaud Lauris , Raffoux Emmanuel , Lambert Juliette , Braun Thorsten , Thomas Xavier , Chantepie Sylvain , Cluzeau Thomas , de Botton Stéphane , Berthon Céline , Boissel Nicolas , Duployez Nicolas , Terré Christine , Peffault de Latour Régis , Michallet Mauricette , Celli-Lebras Karine , Preudhomme Claude , Dombret Hervé
Published: May 2020

In this study, we aimed to refine prognostication of older with acute myeloid leukemia (AML) after intensive chemotherapy. Five hundred and nine patients aged 60 years or older (median age, 68 years) were prospectively enrolled in the intensive Acute Leukemia French Association (ALFA)-1200 trial between 2012 and 2016, and 471 patient samples were submitted to multigene analysis. Mutations in any of 8 genes frequently altered in myelodysplastic syndromes (MDS), including ASXL1, SRSF2, STAG2, BCOR, U2AF1, EZH2, SF3B1, and ZRSR2, defined a secondary AML (sAML)-like disease, as reported. Of the samples analyzed, 48% included sAML-like gene mutations. These mutations were associated with a shorter event-free survival, both overall (hazard ratio, 1.46; 95% confidence interval, 1.19-1.79; P < .001) and within the European LeukemiaNet (ELN)-2017 intermediate-risk subgroup (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28; P = .044), which excludes ASXL1-mutated cases by definition. We therefore included patients with intermediate-risk AML carrying sAML-like mutations in a single high-risk patients group together with adverse-risk patients with AML, whereas other intermediate-risk patients were included in a standard-risk group together with favorable-risk patients (high-risk/standard-risk patient ratio, 1.00). Using this 2-class risk assessment, we observed that transplantation prolonged overall survival from remission in patients with high-risk AML only, not in patients with standard-risk AML. Routine analysis of sAML-like gene mutations may thus improve the definition of high-risk older patients with AML, and better identify the half of older patients who clearly derive survival benefit from allogeneic transplantation in first remission. This trial was registered at www.clinicaltrials.gov as #NCT01966497.
Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML
Authors: Choe Sung , Wang Hongfang , DiNardo Courtney D. , Stein Eytan M. , de Botton Stéphane , Roboz Gail J. , Altman Jessica K. , Mims Alice S. , Watts Justin M. , Pollyea Daniel A. , Fathi Amir T. , Tallman Martin S. , Kantarjian Hagop M. , Stone Richard M. , Quek Lynn , Konteatis Zenon , Dang Lenny , Nicolay Brandon , Nejad Parham , Liu Guowen , Zhang Vickie , Liu Hua , Goldwasser Meredith , Liu Wei , Marks Kevin , Bowden Chris , Biller Scott A. , Attar Eyal C. , Wu Bin
Published: May 2020

Isocitrate dehydrogenase (IDH) 1 and 2 mutations result in overproduction of D-2-hydroxyglutarate (2-HG) and impaired cellular differentiation. Ivosidenib, a targeted mutant IDH1 (mIDH1) enzyme inhibitor, can restore normal differentiation and results in clinical responses in a subset of patients with mIDH1 relapsed/refractory (R/R) acute myeloid leukemia (AML). We explored mechanisms of ivosidenib resistance in 174 patients with confirmed mIDH1 R/R AML from a phase 1 trial. Receptor tyrosine kinase (RTK) pathway mutations were associated with primary resistance to ivosidenib. Multiple mechanisms contributed to acquired resistance, particularly outgrowth of RTK pathway mutations and 2-HG–restoring mutations (second-site IDH1 mutations, IDH2 mutations). Observation of multiple concurrent mechanisms in individual patients underscores the complex biology of resistance and has important implications for rational combination therapy design. This trial was registered at www.clinicaltrials.gov as #NCT02074839
A randomised trial of high-flow nasal cannula in infants with moderate bronchiolitis
Authors: Durand Philippe , Guiddir Tamazoust , Kyheng Christèle , Blanc Florence , Vignaud Olivier , Epaud Ralph , Dugelay Frédéric , Breant Isabelle , Badier Isabelle , Degas-Bussière Vanessa , Phan Florence , Soussan-Banini Valérie , Lehnert Agnès , Mbamba Célestin , Barrey Catherine , Tahiri Cédric , Decobert Marion , Saunier-Pernaudet Marie , Craiu Irina , Taveira Mélanie , Gajdos Vincent
Published: May 2020

Background

The objective was to determine whether high-flow nasal cannula (HFNC), a promising respiratory support in infant bronchiolitis, could reduce the proportion of treatment failure requiring escalation of care.

Methods

In this randomised controlled trial, we assigned infants aged <6 months who had moderate bronchiolitis to receive either HFNC at 3 L·kg−1·min−1or standard oxygen therapy. Crossover was not allowed. The primary outcome was the proportion of patients in treatment failure requiring escalation of care (mostly noninvasive ventilation) within 7 days following randomisation. Secondary outcomes included rates of transfer to the paediatric intensive care unit (PICU), oxygen, number of artificial nutritional support-free days and adverse events.

Results

The analyses included 268 patients among the 2621 infants assessed for inclusion during two consecutive seasons in 17 French paediatric emergency departments. The percentage of infants in treatment failure was 14% (19 out of 133) in the study group, compared to 20% (27 out of 135) in the control group (OR 0.66, 95% CI 0.35–1.26; p=0.21). HFNC did not reduce the risk of admission to PICU (21 (15%) out of 133 in the study groupversus26 (19%) out of 135 in the control group) (OR 0.78, 95% CI 0.41–1.41; p=0.45). The main reason for treatment failure was the worsening of modified Wood clinical asthma score (m-WCAS). Short-term assessment of respiratory status showed a significant difference for m-WCAS and respiratory rate in favour of HFNC. Three pneumothoraces were reported in the study group.

Conclusions

In patients with moderate bronchiolitis, there was no evidence of lower rate of escalating respiratory support among those receiving HFNC therapy.
Self-analysis of repeat proteins reveals evolutionarily conserved patterns
Authors: Merski Matthew , Młynarczyk Krzysztof , Ludwiczak Jan , Skrzeczkowski Jakub , Dunin-Horkawicz Stanisław , Górna Maria W.
Published: May 2020

Background

Protein repeats can confound sequence analyses because the repetitiveness of their amino acid sequences lead to difficulties in identifying whether similar repeats are due to convergent or divergent evolution. We noted that the patterns derived from traditional “dot plot” protein sequence self-similarity analysis tended to be conserved in sets of related repeat proteins and this conservation could be quantitated using a Jaccard metric.

Results

Comparison of these dot plots obviated the issues due to sequence similarity for analysis of repeat proteins. A high Jaccard similarity score was suggestive of a conserved relationship between closely related repeat proteins. The dot plot patterns decayed quickly in the absence of selective pressure with an expected loss of 50% of Jaccard similarity due to a loss of 8.2% sequence identity. To perform method testing, we assembled a standard set of 79 repeat proteins representing all the subgroups in RepeatsDB. Comparison of known repeat and non-repeat proteins from the PDB suggested that the information content in dot plots could be used to identify repeat proteins from pure sequence with no requirement for structural information. Analysis of the UniRef90 database suggested that 16.9% of all known proteins could be classified as repeat proteins. These 13.3 million putative repeat protein chains were clustered and a significant amount (82.9%) of clusters containing between 5 and 200 members were of a single functional type.

Conclusions

Dot plot analysis of repeat proteins attempts to obviate issues that arise due to the sequence degeneracy of repeat proteins. These results show that this kind of analysis can efficiently be applied to analyze repeat proteins on a large scale.
Cloning, molecular and functional characterization by overexpression in Arabidopsis of MAPKK genes from grapevine (Vitis vinifera)
Authors: Wang Gang , Liang Ying-hai , Zhang Ji-yu , Cheng Zong-Ming
Published: May 2020

Background

The mitogen-activated protein kinases (MAPKs), as a part of the MAPKKK-MAPKK-MAPK cascade, play crucial roles in plant development as an intracellular signal transduction pathway to respond various environmental signals. However, few MAPKK have been functionally characterized in grapevine.

Results

In the study, five MAPKK (MKK) members were identified in grapevine (cultivar ‘Pinot Noir’), cloned and designated as VvMKK1-VvMKK5. A phylogenetic analysis grouped them into four sub-families based on the similarity of their conserved motifs and gene structure to Arabidopsis MAPKK members. qRT-PCR results indicated that the expression of VvMKK1, VvMKK2, VvMKK4, and VvMKK5 were up-regulated in mature leaf and young blades, and roots, but exhibited low expression in leaf petioles. VvMKK2, VvMKK3, and VvMKK5 genes were differentially up-regulated when grapevine leaves were inoculated with spores of Erisyphe necator, or treated with salicylic acid (SA), ethylene (ETH), H2O2, or exposed to drought, indicating that these genes may be involved in a variety of signaling pathways. Over expression of VvMKK2 and VvMKK4 genes in transgenic Arabidopsis plants resulted in the production of seeds with a significantly higher germination and survival rate, and better seedling growth under stress conditions than wild-type plants. Overexpression of VvMKK2 in Arabidopsis improved salt and drought stress tolerance while overexpression of VvMKK4 only improved salt stress tolerance.

Conclusions

Results of the present investigation provide a better understanding of the interaction and function of MAPKKK-MAPKK-MAPK genes at the transcriptional level in grapevine and led to the identification of candidate genes for drought and salt stress in grapes.
Transcriptomic and physiological analyses of rice seedlings under different nitrogen supplies provide insight into the regulation involved in axillary bud outgrowth
Authors: Wang Rongna , Qian Junjie , Fang Zhongming , Tang Jihua
Published: May 2020

Background

N is an important macronutrient required for plant development and significantly influences axillary bud outgrowth, which affects tillering and grain yield of rice. However, how different N concentrations affect axillary bud growth at the molecular and transcriptional levels remains unclear.

Results

In this study, morphological changes in the axillary bud growth of rice seedlings under different N concentrations ranging from low to high levels were systematically observed. To investigate the expression of N-induced genes involved in axillary bud growth, we used RNA-seq technology to generate mRNA transcriptomic data from two tissue types, basal parts and axillary buds, of plants grown under six different N concentrations. In total, 10,221 and 12,180 DEGs induced by LN or HN supplies were identified in the basal parts and axillary buds, respectively, via comparisons to expression levels under NN level. Analysis of the coexpression modules from the DEGs of the basal parts and axillary buds revealed an abundance of related biological processes underlying the axillary bud growth of plants under N treatments. Among these processes, the activity of cell division and expansion was positively correlated with the growth rate of axillary buds of plants grown under different N supplies. Additionally, TFs and phytohormones were shown to play roles in determining the axillary bud growth of plants grown under different N concentrations. We have validated the functions of OsGS1;2 and OsGS2 through the rice transgenic plants with altered tiller numbers, illustrating the important valve of our transcriptomic data.

Conclusion

These results indicate that different N concentrations affect the axillary bud growth rate, and our study show comprehensive expression profiles of genes that respond to different N concentrations, providing an important resource for future studies attempting to determine how axillary bud growth is controlled by different N supplies.
Psychometric properties of measures of substance use: a systematic review and meta-analysis of reliability, validity and diagnostic test accuracy
Authors: Santos Glenn-Milo , Strathdee Steffanie A. , El-Bassel Nabila , Patel Poonam , Subramanian Divya , Horyniak Danielle , Cook Ryan R. , McCullagh Charlotte , Marotta Phillip , Choksi Foram , Kang Brian , Allen Isabel , Shoptaw Steven
Published: May 2020

Background

Synthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse.

Methods

We conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value. We used meta-analytic techniques to generate pooled summary estimates for these outcomes using random effects and hierarchical logistic regression models.

Results

Findings across 387 paper revealed that overall, 65% of pooled estimates for alpha were in the range of fair-to-excellent; 44% of estimates for kappa were in the range of fair-to-excellent. In addition, 69, 97, 37 and 96% of pooled estimates for sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were in the range of moderate-to-excellent.

Conclusion

We conclude that many substance use measures had pooled summary estimates that were at the fair/moderate-to-excellent range across different psychometric outcomes. Most scales were conducted in English, within the United States, highlighting the need to test and validate these measures in more diverse settings. Additionally, the majority of studies had high risk of bias, indicating a need for more studies with higher methodological quality.
Association between antipsychotic drug dose and length of clinical notes: a proxy of disease severity?
Authors: Sørup Freja Karuna Hemmingsen , Brunak Søren , Eriksson Robert
Published: May 2020

Background

Most structured clinical data, such as diagnosis codes, are not sufficient to obtain precise phenotypes and assess disease burden. Text mining of clinical notes could provide a basis for detailed profiles of phenotypic traits. The objective of the current study was to determine whether drug dose, regardless of polypharmacy, is associated with the length of clinical notes, and to determine the frequency of adverse events per word in clinical notes.

Methods

In this observational study, we utilized restricted-access data from an electronic patient record system. Using three methods (defined daily dose, olanzapine equivalents, and chlorpromazine equivalents) we calculated antipsychotic dose equivalents and compared these with the number of words recorded per treatment day. For each normalization method, the frequencies of adverse events per word in manually curated samples were compared to dose intervals.

Results

The length of clinical notes per treatment day was positively associated with the prescribed dose for all normalization methods. The number of adverse events per word was stable over the analyzed dose spectrum.

Conclusions

Assuming that drug dose increases with the severity of disease, the length of clinical notes can serve as a proxy for disease severity. Due to the near-linear relationship, correction of daily word count is unnecessary when text mining for potential adverse drug reactions.