bluuebunny/crossref_metadata_2025_split huggingface dataset:
The case of the missing royalty stacking in the world mobile wireless industry
Authors: Galetovic Alexander , Gupta Kirti 
Published: December 2019

AbstractWe build an equilibrium royalty stacking model that links the number of standard-essential patent (SEP) holders with the equilibrium quantity, price and cumulative royalty. We show that all observable implications of the theory are inconsistent with the data from the world mobile wireless industry. In this industry, the number of SEP holders grew from 2 in 1994 to 130 in 2013. Royalty stacking theory predicts falling or stagnant output, rising selling prices, and rising or stagnant quality-adjusted prices. By contrast, between 1994 and 2013 worldwide yearly device sales grew 62-fold, at an average rate of 20.1% per year, and both selling and quality-adjusted prices fell fast over time. Controlling for technological generation, the real average selling price of a device fell between -11.4% and -24.8% per year. Similarly, under conservative parametrizations, royalty stacking theory predicts royalty yields, which are more than an order of magnitude larger than the observed average cumulative royalty yield charged by SEP holders in practice, which hovers between 3% and 3.5%. A theory based on Lerner and Tirole’s (2015, J. Political Econ., 123(3), 547–586) within-functionality competition yields observable implications consistent with the observed facts. If all the technologies protected by SEPs have meaningful substitutes that cap the royalty that any SEP holder can charge, then the cumulative royalty is independent of demand parameters in the downstream market and can be as low as the observed average cumulative royalty yield. Moreover, if the product market is competitive and technological progress is fast, then prices follow costs, quality-adjusted prices protractedly fall, and sales grow fast.
Microcredit Contracts, Risk Diversification and Loan Take-Up
Authors: Attanasio Orazio , Augsburg Britta , De Haas Ralph 
Published: December 2019

Abstract
We study theoretically and empirically the demand for microcredit under different liability arrangements and risk environments. A theoretical model shows that the demand for joint-liability loans can exceed that for individual-liability loans when risk-averse borrowers value their long-term relationship with the lender. Joint liability then offers a way to diversify risk and reduce the chance of losing access to future loans. We also show that the demand for loans depends negatively on the riskiness of projects. Using data from a randomised controlled trial in Mongolia we find that these model predictions hold true empirically. In particular, we use innovative data on subjective risk perceptions to show that expected project risk negatively affects the demand for loans. In line with an insurance role of joint-liability contracts, this effect is muted in villages where joint-liability loans are available.
Severe heterotopic ossification post total knee arthroplasty in a patient with rheumatoid arthritis: a case report
Authors: Alturki Abdullah A , Aldeghaither Sarah A , Alhandi Ali A 
Published: December 2019

Abstract
Stiffness following total knee arthroplasty (TKA) can be a devastating complication to the patient by limiting his function. Various causes have been reported in the literature, including heterotopic ossification (HO). HO is one of the rarely reported complication of TKA characterized by deposition of bone cells in non-skeletal tissue. This is a case of 32-year-old female known to have rheumatoid arthritis with history of TKA 4-years-ago complaining of right knee pain and restricted range of motion. She was later found to have HO and was treated with a revision TKA. In conclusion, the incidence and outcome of HO following total knee replacement in patients with RA remains underexplored topic in the literature.
Mental Health During Naval Deployment: The Protective Role of Family Support
Authors: Nordmo Morten , Hystad Sigurd William , Sanden Sverre , Johnsen Bjørn Helge 
Published: December 2019

AbstractIntroductionMinor mental health problems among service members deployed in combat areas are relatively common, but social support is a protective factor. With the advent of digital communication, as well as more frequent family separations, a stable family support system may be more important than before. In this exploratory study, we aimed to test the relationship between perceived family support and the development of minor psychiatric symptoms during a 4-month naval counter piracy mission in the Gulf of Aden.Materials and MethodsWe measured minor mental health problems with the general health questionnaire 12 (GHQ-12) and family support at three intervals, 3 weeks before deployment, 2 months into the mission, and at the end of deployment. We used mixed multilevel regression analysis to analyze the main effects of family support and time, as well as their interaction. All analyses were controlled for military rank.ResultsWe found that minor psychiatric symptoms increased at both midway (B = 0.51, P &lt; 0.05) and toward the end of the mission (B = 0.72, P &lt; 0.01). The results also showed that receiving more family support is associated with fewer psychiatric symptoms (B = −0.87, P &lt; 0.01). Family support also moderated the development of symptoms toward the end of the mission (B = −0.73, P &lt; 0.01). The buffering effect was such that service members with a high degree of family support experienced no increase in minor psychiatric symptoms during the deployment.ConclusionsThe results indicate that naval deployment is associated with a small increase in minor mental health problems and that having a high degree of family support buffers this effect. Efforts to increase support among military families may positively influence the wellbeing of naval sailors during combat missions.
Horizontal Gene Transfer Phylogenetics: A Random Walk Approach
Authors: Sevillya Gur , Doerr Daniel , Lerner Yael , Stoye Jens , Steel Mike , Snir Sagi 
Published: December 2019

AbstractThe dramatic decrease in time and cost for generating genetic sequence data has opened up vast opportunities in molecular systematics, one of which is the ability to decipher the evolutionary history of strains of a species. Under this fine systematic resolution, the standard markers are too crude to provide a phylogenetic signal. Nevertheless, among prokaryotes, genome dynamics in the form of horizontal gene transfer (HGT) between organisms and gene loss seem to provide far richer information by affecting both gene order and gene content. The “synteny index” (SI) between a pair of genomes combines these latter two factors, allowing comparison of genomes with unequal gene content, together with order considerations of their common genes. Although this approach is useful for classifying close relatives, no rigorous statistical modeling for it has been suggested. Such modeling is valuable, as it allows observed measures to be transformed into estimates of time periods during evolution, yielding the “additivity” of the measure. To the best of our knowledge, there is no other additivity proof for other gene order/content measures under HGT. Here, we provide a first statistical model and analysis for the SI measure. We model the “gene neighborhood” as a “birth–death–immigration” process affected by the HGT activity over the genome, and analytically relate the HGT rate and time to the expected SI. This model is asymptotic and thus provides accurate results, assuming infinite size genomes. Therefore, we also developed a heuristic model following an “exponential decay” function, accounting for biologically realistic values, which performed well in simulations. Applying this model to 1,133 prokaryotes partitioned to 39 clusters by the rank of genus yields that the average number of genome dynamics events per gene in the phylogenetic depth of genus is around half with significant variability between genera. This result extends and confirms similar results obtained for individual genera in different manners.
Synergistic activity of mTORC1/2 kinase and MEK inhibitors suppresses pediatric low-grade glioma tumorigenicity and vascularity
Authors: Arnold Antje , Yuan Ming , Price Antionette , Harris Lauren , Eberhart Charles G , Raabe Eric H 
Published: December 2019

Abstract

Background
Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor. Many patients with unresectable or recurrent/refractory tumors have significant lifelong disability. The majority of pLGG have mutations increasing the activity of the Ras/mitogen-activated protein kinase (MAPK) pathway. Activation of mammalian target of rapamycin (mTOR) is also a hallmark of pLGG. We therefore hypothesized that the dual target of rapamycin complexes 1 and 2 (TORC1/2) kinase inhibitor TAK228 would synergize with the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib in pLGG.

Methods
We tested TAK228 and trametinib in patient-derived pLGG cell lines harboring drivers of pLGG including BRAFV600E and neurofibromatosis type 1 loss. We measured cell proliferation, pathway inhibition, cell death, and senescence. Synergy was analyzed via MTS assay using the Chou–Talalay method. In vivo, we tested for overall survival and pathway inhibition and performed immunohistochemistry for proliferation and vascularization. We performed a scratch assay and measured angiogenesis protein activation in human umbilical vein endothelial cells (HUVECs).

Results
TAK228 synergized with trametinib in pLGG at clinically relevant doses in all tested cell lines, suppressing proliferation, inducing apoptosis, and causing senescence in a cell line–dependent manner. Combination treatment increased median survival by 70% and reduced tumor volume compared with monotreatment and control cohorts. Vascularization of tumors decreased as measured by CD31 and CD34. Combination treatment blocked activation of focal adhesion kinase (FAK) and sarcoma proto-oncogene non-receptor tyrosine kinase (SRC) in HUVEC cells and reduced HUVEC migration compared with each drug alone.

Conclusions
The combination of TAK228 and trametinib synergized to suppress the growth of pLGG. These agents synergized to reduce tumor vascularity and endothelial cell growth and migration by blocking activation of FAK and SRC.
A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)
Authors: Cloughesy Timothy F , Brenner Andrew , de Groot John F , Butowski Nicholas A , Zach Leor , Campian Jian L , Ellingson Benjamin M , Freedman Laurence S , Cohen Yael C , Lowenton-Spier Noa , Rachmilewitz Minei Tamar , Fain Shmueli Shifra ,   GLOBE Study Investigators, Wen Patrick Y , Avgeropoulos Nicholas , Beck Joseph , Benkers Tara , Bokstein Felix , Brenner Andrew , Burton Eric , Butowski Nicholas , Campian Jian , Carrillo Jose , Cloughesy Timothy , de Groot John , De Robles Paula , Drappatz Jan , Dunbar Irine , Fink Karen , Groves Morris , Han Xiaosi , Adila Hormigo , Jensen Randy , Kowalska Agnieszka , Kumthekar Pyriya , Lee Mijung , Lesser Glenn , Lossos Alexander , Lukas Rimas , Macdonald David , Mammoser Aaron , Mechtler Laszlo , Mohile Nimish , Nagpal Seema , Nicholas Garth , Kreisl Teri , Pan Edward , Peak Scott , Pearlman Michael , Perry James , Peterson Richard , Piccioni David , Robins Henry , Ronan Lara , Salacz Michael , Schiff David , Tran David , Zach Leor , Tzuk-Shina Tzahala , Walbert Tobias , Wen Patrick , Youst Shlomit 
Published: December 2019

AbstractBackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91–1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3–5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405
The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala
Authors: Samayoa B , Aguirre L , Bonilla O , Medina N , Lau-Bonilla D , Mercado D , Moller A , Perez J C , Alastruey-Izquierdo A , Arathoon E , Denning D W , Rodríguez-Tudela J L ,   “Fungired”, López Pérez Oscar Eduardo , Ortiz Barrientos Brenan , Reyes Muñoz Vilma Alejandrina , Sajché Aguilar Gladys , Méndez Andrade Aura Marina , de León Luis Roberto Santa Marina , Gómez Alcázar Ana Lucía , González Eduardo Celada , Quiñónez M Gustavo A , Cuyuch Sontay Germán Orlando , Contreras Marín Alba Virtud , Fong Araujo María de Lourdes , Mazariegos L Claudia , Guzmán Brenda 
Published: December 2019

Abstract

Background
A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH).

Methods
Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for &gt;90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed.

Results
In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had &lt;200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200–350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free.

Conclusions
The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of &lt;350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.
TREATMENT OF INTERNAL CAROTID ANEURYSMS USING PIPELINE EMBOLIZATION DEVICES: MEASURING THE RADIATION DOSE OF THE PATIENT AND DETERMINING THE FACTORS AFFECTING IT
Authors: Kawauchi Satoru , Chida Koichi , Moritake Takashi , Hamada Yusuke , Matsumaru Yuji , Tsuruta Wataro , Sato Masayuki , Hosoo Hisayuki , Sun Lue 
Published: December 2019

Abstract
The purpose of this study was to measure the peak skin dose (PSD) and bilateral lens doses using radiophotoluminescence glass dosimeters and to determine the factors influencing the radiation dose in cases of cerebral aneurysm treated with pipeline embolization devices (PEDs). The cumulative dose, PSD and right and left lens doses were 3818.1 ± 1604.6, 1880.0 ± 723.0, 124.8 ± 49.2 and 180.7 ± 124.8 mGy, respectively. Using multivariate analysis, body mass index (p &lt; 0.01; odds ratio (OR) = 1.806; 95% confidence interval (CI) = 1.007–3.238) and deployment time of PED (p &lt; 0.05; OR = 1.107; 95% CI = 1.001–1.224) were found to be the independent predictors of PSD exceeding 2 Gy. Measures such as collimation of the radiation field and optimization of radiation dose should be taken to reduce the radiation to the patient.
High frequency of Exon 20 S768I EGFR mutation detected in malignant pleural effusions: a poor prognosticator of NSCLC?
Authors: D’Souza George , Dhar Chirag , Kyalanoor Vishal , Yadav Lokendra , Sharmra Mugdha , Nawaz S Mohammad , Srivastava Sweta 
Published: December 2019

AbstractLung cancer is the cause of a fourth of all cancer-related deaths. About a third of all lung adenocarcinoma tumours harbour mutations on exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene. Detection of these mutations allows for targeted therapies in the form of EGFR Tyrosine kinase inhibitors. In our study, we utilized malignant pleural effusions (MPEs) as “liquid biopsies” to detect EGFR mutations when tissue biopsies were unavailable. We showed that a direct sequencing approach was likely to miss SNVs in MPEs. We then optimized an EGFR mutant-specific quantitative polymerase chain reaction-based assay and piloted it on n=10 pleural effusion samples (1 non-malignant pleural effusion as a negative control). 5/9 (55.55%) samples harboured EGFR mutations with 2/9 (22.22%) being exon 19 deletions and 3/9 (33.33%) had the S768I exon 20 mutation. The frequency of the S768I SNV in our study was significantly higher than that observed in other studies (∼0.3%). Utilizing publicly available cBioPortal data, we report that patients with the S768I SNV had a shorter median survival time, progression-free survival time and lower tumor mutation count compared to patients with other EGFR mutations. These data suggest that this point mutation predicts poor prognosis as a result of aggressive disease, though studies in larger cohorts are necessary to confirm these findings. The high frequency of S768I mutations seen in our study also suggests that cancer cells harbouring these mutations may be superior in their ability to migrate, home or reside in pleural fluid.
Whole exome-trio analysis reveals rare variants associated with Congenital Pouch Colon
Authors: Gupta Sonal , Mathur Praveen , Mishra Ashwani Kumar , Medicherla Krishna Mohan , Suravajhala Prashanth 
Published: December 2019

AbstractAnorectal malformations (ARM) are individually common but Congenital Pouch Colon (CPC), a rare anorectal anomaly causes a dilated pouch in genitourinary tract. We have earlier attempted to understand the clinical genetic makeup of CPC and identified genes responsible for the disease using whole exome sequencing (WES). Here we report our studies of CPC, by identifying de novo heterozygous missense mutations in 16 proband-parent trios and further discover variants of unknown significance which could provide insights into CPC manifestation and its etiology. Our study confirms candidate mutations in genes, viz. C7orf57, C10orf120, C9orf84 and MUC16, CTC1 particularly emphasizing the role of hypothetical genes or open reading frames causing this developmental disorder. Variant validation revealed disease causing mutations associated with CPC and genitourinary diseases which could close the gaps of surgery in bringing intervention in therapies.
Using the Bayesian credible subgroups method to identify populations benefiting from treatment: An application to the Look AHEAD trial
Authors: Coonan Anna , Forbes John , Schnell Patrick , Smith Joel 
Published: December 2019

AbstractTraditionally, subgroup analyses are used to assess whether patient characteristics moderate treatment effectiveness with general disregard for issues of multiplicity. Using data from The Action for Health in Diabetes (Look AHEAD) trial in the United States, we aim to identify a subgroup where all of its types of members experience a treatment benefit defined as reducing the likelihood of a major cardiovascular event under an intensive lifestyle and weight-loss intervention. We apply the credible subgroups method to a Bayesian logistic model with a conservative prior that is sceptical of large treatment effect heterogeneity. The covariate profiles for which there is sufficient evidence of treatment benefit are, coarsely, middle-aged women, in poor subjective general health and with moderately to poorly controlled diabetes. There is at least 80% posterior probability that the conditional average treatment effect is positive for all covariate profiles fitting this description, which account for 0.5% of trial participants. Conversely, the covariate profiles that are likely to be associated with no benefit are middle aged and older men in excellent subjective general health, with well-controlled diabetes. These profiles apply to less than 2% of trial participants. More information is required to determine treatment benefit or no benefit for the remainder of the trial population.
Assessment and Utilization of Patient-Reported Outcomes Measures to Improve Cardiovascular Disease Prevention
Authors: Finneran Phoebe A , Sanborn Tinamarie , Guo Xiao , Traynor Kate C , Jaff Michael R. , Natarajan Pradeep 
Published: December 2019

AbstractBackgroundThe American Heart Association’s Life’s Simple 7 (LS7) consist of clinical factors and health-related behaviors associated with cardiovascular health. The prevalence of these health factors among patients seeking specialized cardiovascular care is unknown. We sought to quantify patient-reported cardiovascular risk among those seeking specialized cardiovascular care and implement tailored quality improvement interventions.Methods and ResultsPatients cared for by cardiovascular specialists at an academic medical center were surveyed with a modified LS7. We compared the prevalence of optimal health factors by atherosclerotic cardiovascular disease (ASCVD) status. Recent smokers or patients with ASCVD reporting non-adherence to antiplatelets/statins were contacted.Surveys for 5,950 patients were collected during 2014 to 2016. The mean (SD) age was 64 (15) years, 2613 (44%) were women, and 3478 (58%) had ASCVD. Only 34 (0.6 %) achieved ideal status for all 7 factors, which did not differ by ASCVD status (P=0.48). Of 404 (6.8%) reporting recent smoking, 94/404 (23.3%) were successfully contacted, and 71/404 (17.6%) accepted support. Among those with ASCVD, 84 (2.4%) reported not taking a statin or antiplatelet without contraindications.ConclusionsThe prevalence of optimal health factors, including health-related behaviors, among patients cared for by cardiovascular specialists remains low. Assessment of patient-reported outcomes facilitates scalable interventions to improve cardiovascular disease prevention.