bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 study of CA-4948, a novel inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) in patients (pts) with r/r non-Hodgkin lymphoma.
Authors: Rosenthal Allison Claire , Tun Han W. , Younes Anas , Nowakowski Grzegorz S. , Lunning Matthew Alexander , Patel Krish , Landsburg Daniel Jeffrey , Martell Robert E. , Leslie Lori Ann 
Published: February 2020

e19055 Background: IRAK4 is a signaling modulator of Toll-like receptors (TLRs) and members of the IL-1R family. TLR/IL-1R activity is frequently dysregulated in NHL, including DLBCL and Waldenström macroglobulinemia (WM). CA-4948, an oral inhibitor of IRAK4, has demonstrated anti-tumor activity in preclinical models. Methods: Dose finding cohorts (3+3 design) will test QD or BID dosing schedule in pts with R/R NHL. Dose expansion will occur in 2 cohorts of R/R NHL with or without MYD88 mutation at the RP2D or MTD. Key eligibility criteria: age ≥ 18 years, ECOG ≤1, and adequate organ function. Objectives: safety, MTD and RP2D (primary); PK and anti-tumor activity (secondary); exploratory biomarkers and PD effects. Plasma cytokine levels are being evaluated post ex-vivo TLR stimulation in whole blood. Results: 13 pts have been treated (6 at 50 mg QD; 3 at 100 mg QD; 4 at 50 mg BID). Tumor types included DLBCL (7), FL (5), WM (1). The most frequent treatment-emergent AEs (≥10% of pts) were fatigue (23%), conjunctivitis, constipation, neutrophil count decrease, white blood cell count decrease (each 15%). One pt treated at 100 mg QD experienced Gr 3 rash which resolved following oral steroid treatment; dose reduction to 50 mg QD was tolerated without flare up. One SAE of disease progression occurred. 9 pts completed the DLT evaluation period thru Cycle 2 including 2 ongoing in Cycle 4 and 6. Preliminary PK showed that CA-4948 is rapidly absorbed with maximum plasma concentration observed 1.0 to 4.0 hrs post administration. T1/2 in plasma was about 6 hrs. Minimal to no accumulation was observed following multiple doses. Plasma exposures were dose proportional. Preliminary PD data showed, similar to murine studies, on target reduction of NF-kB-associated factors such as IL-6 post-treatment from pts with complete sample sets (N = 8). Conclusions: Current dose/schedule is well tolerated with preliminary PK and PD effects at the initial dose level. MTD has not been reached. Clinical trial information: NCT03328078.
Eating versus skipping breakfast has no discernible effect on obesity-related anthropometric outcomes: a systematic review and meta-analysis
Authors: Bohan Brown Michelle M. , Milanes Jillian E. , Allison David B. , Brown Andrew W. 
Published: February 2020

Background:Whether one should eat or skip breakfast for weight is of continued interest in both the scientific and lay communities. Our objective was to systematically review and meta-analyze causal effects of eating versus skipping breakfast on obesity-related anthropometric outcomes in humans.Methods:AltHealthWatch, CINAHL, Proquest Theses and Dissertations Global, PsycInfo, and Scopus were searched for obesity- and breakfast-related terms in humans (final search: 02 JAN 2020). Studies needed to isolate eating versus skipping breakfast in randomized controlled trials. Mean differences were synthesized using inverse variance random effects meta-analysis for each outcome measured in more than one study. Positive estimates indicate higher outcomes in breakfast conditions (e.g., weight gain). Leave-one-out analysis was used for sensitivity. Risk of bias was assessed using the Cochrane risk of bias tool.Results:Ten articles (12 comparisons) were included. Study lengths spanned 6 days to 16 weeks. Conditions included recommendations to eat versus skip breakfast, or provision of some or all meals. 95% confidence intervals of all main analyses included the null value of no difference for each outcome: body weight (0.17 kg [-0.40,0.74], k=12, n=486, I2=74.4), BMI (0.08 kg/m2[-0.10,0.26, k=8, n=395, I2=53.9), body fat percentage (-0.27% [-1.01,0.47], k=6, n=179, I2=52.4), fat mass (0.24 kg [-0.21,0.69], k=6, n=205, I2=0.0), lean mass (0.18 kg [-0.08,0.44], k=6, n=205, I2=6.7), waist circumference (0.18 cm [-1.77,2.13], k=4, n=102, I2=78.7), waist:hip ratio (0.00 [-0.01,0.01], k=4, n=102, I2=8.0), sagittal abdominal diameter (0.19 cm [-2.35,2.73], k=2, n=56, I2=0.0), and fat mass index (0.00 kg/m2[-0.22,0.23], k=2, n=56, I2=0.0). One study reported muscle mass and total body water percentage. Leave-one-out analysis did not indicate substantial influence of any one study.Conclusions:There was no discernible effect of eating or skipping breakfast on obesity-related anthropometric measures when pooling studies with substantial design heterogeneity and sometimes statistical heterogeneity.Registration:PROSPEROCRD42016033290.
Stability and Synchronization of a Fractional Neutral Higher-Order Neural Network System
Authors: Tatar N.-E. 
Published: February 2020

Abstract
We discuss the stability and synchronization of some neural network systems with more than one feature. They are of higher-order, of fractional order and also involving delays of neutral type. Each one of these features presents substantial difficulties to overcome. We prove stability and synchronization of Mittag-Leffler type. This rate is fairly reasonable in case of fractional order. This leads us to prove a neutral fractional version of the well-known Halanay inequality which is interesting by itself. Another feature of the present work is the treatment of unbounded activation functions. The condition of uniform boundedness of the activation functions was commonly used in the literature.
A Pedagogical Perspective on the Definite and the Indefinite Article in the Romanian Language. Challenges for Foreign Learners
Authors: Ivancu Ovidiu 
Published: February 2020

All Romance languages have developed the definite and the indefinite article via the Vulgar Latin (Classical Latin did not use articles), the language of the Roman colonists. According to Joseph H. Greenberg (1978), the definite article predated the indefinite one by approximately two centuries, being developed from demonstratives through a complex process of grammaticalization. Many areas of nowadays` Romania were incorporated into the Roman Empire for about 170 years. After two military campaign, the Roman emperor Trajan conquered Dacia, east of Danube.The Romans imposed their own administration and inforced Latin as lingua franca.The language of the colonists, mixed with the native language and, later on, with various languages spoken by the many migrant populations that followed the Roman retreat resulted in a new language (Romanian), of Latin origins. The Romanian language, attested in the 16th Century, in documents written by foreign travellers, uses four different types of articles. Being a highly inflected language, Romanian changes the form of the articles according to the gender, the number and the case of the noun As compared to the other Romance languages, Romanian uses the definite article enclitically. Thus, the definite article and the noun constitute a single word. The present paper aims at discussing, analysing and providing an overview of the use of definite and indefinite articles. The general norm and its various exceptions are examined from a broader perspective, synchronically and diachronically. The pedagogical perspective is meant to offer a comprehensible synthesis to foreign learners.
Why There Is a Need for an International Organ to Try the Crime of Terrorism - Past Experiences and Future Opportunities
Authors: Kleczkowska Agata 
Published: February 2020

Abstract
This paper suggests that the crime of terrorism requires the establishment of an international organ to prosecute the perpetrators of the crime and there is a need to enable the prosecution of the crime of terrorism as a specific new type of international crime. In advancing this thesis, the paper is divided into three parts. The first part briefly defines the notion of terrorism, while the second discusses the international legal instruments and practices when it comes to prosecution of the crime of terrorism. It starts with the first failed attempts to define and prosecute the crime of terrorism. Next, it discusses the jurisdiction of different international courts and tribunals over the crime of terrorism. The third part presents the specific case of the Polish domestic legislation regulating the crime of terrorism in order to demonstrate that States which so far have not been affected in a major way by terrorism may have little experience in creating comprehensive legislation, yet they still may have to deal with perpetrators of the crime. This is why both a comprehensive legal instrument and an international organ with jurisdiction over the crime of terrorism are necessary.
All together now: aggregating multiple records to develop a person-based dataset to integrate and enhance infectious disease surveillance in Ontario, Canada
Authors: Whelan Michael , Renda Christina , Hohenadel Karin , Buchan Sarah , Murti Michelle 
Published: February 2020

Abstract
Setting
Syndemics occur when two or more health conditions interact to increase morbidity and mortality and are exacerbated by social, economic, environmental, and political factors. Routine provincial surveillance in Ontario assesses and reports on the epidemiology of single infectious diseases separately. Therefore, we aimed to develop a method that allows disease overlaps to be examined routinely as a path to better understanding and addressing syndemics in Ontario.

Intervention
We extracted data for individuals with a record of chlamydia, gonorrhea, infectious syphilis, hepatitis B and C, HIV/AIDS, invasive group A streptococcal disease (iGAS), or tuberculosis in Ontario’s reportable disease database from 1990 to 2018. We transformed the data into a person-based integrated surveillance dataset retaining individuals (clients) with at least one record between 2006 and 2018.

Outcomes
The resulting dataset had 659,136 unique disease records among 470,673 unique clients. Of those clients, 23.1% had multiple disease records with 50 being the most for one client. We described the frequency of disease overlaps; for example, 34.7% of clients with a syphilis record had a gonorrhea record. We quantified known overlaps, finding 1274 clients had gonorrhea, infectious syphilis, and HIV/AIDS records, and potentially emerging overlaps, finding 59 clients had HIV/AIDS, hepatitis C, and iGAS records.

Implications
Our novel person-based integrated surveillance dataset represents a platform for ongoing in-depth assessment of disease overlaps such as the relative timing of disease records. It enables a more client-focused approach, is a step towards improved characterization of syndemics in Ontario, and could inform other jurisdictions interested in adopting similar approaches.
Mitochondrial dysfunctions and antihypoxants
Authors: Novikov Vasiliy E. , Levchenkova Olga S. , Ivantsova Elena N. , Vorobieva Victoria V. 
Published: February 2020

Mitochondrial dysfunctions (an impaired energy metabolism in the mitochondria) are essential in a pathogenesis of many diseases.
Aim. The analysis of various mitochondrial dysfunction (MD) type study, as well as evaluation of drugs with an antihypoxic effect in their treatment.
Methods. Collection, systematization and analysis of experimental and clinical data of current scientific research about the problem.
Results. The mitochondrial dysfunctions can be caused by genetic disorders of the mitochondrial or nuclear genome (the primary MD or the mitochondrial diseases), as well as structural, functional and biochemical defects of mitochondria caused by other diseases (the secondary MD). MD are characterized by impaired tissue respiration, ATP synthesis deficiency and decreased energy metabolism. The clinical implications of MD are polysystemic and polymorphic. One of the biochemical sign of MD is the lactic acidosis. There are certain difficulties with the early diagnosis of primary MD. It is suggested to use complete exome sequencing among patients with a clinical suspicion on mitochondrial disease. The energotropic pharmacotherapy including drugs with an antihypoxic effect is used for MD treatment. It is more rational to use the drug combination that influences different stages of energy production. The combinations of L-carnitine, coenzyme Q10, cytochrome C and succinate-containing drugs are frequently used for MD. However, the usage of energotropic and antihypoxic drugs is not able to cure the patients and stop the progression of all disease displays.
Conclusion. MD are a multidisciplinary problem, therefore, doctors of any speciality must be competent in the MD diagnosis and treatment. The use of energotropic agents in the MD treatment requires further research. Numerous issues remain open (daily drug doses choice, treatment duration, rational combinations). The phenotype variability and the uniqueness of diagnosed cases, clinical and genetic differences between patient groups with mitochondrial diseases fail to create homogeneous samplings for therapy effectiveness and safety analysis. The literature data are the results of different degrees of reliability. The international efforts are needed to unify studies of related mitochondrial disorders, which, in combination with a constant improvement of MD pathogenesis knowledge will allow to develop more effective treatment regimens.
Case report: Upper Lip Reconstruction after Lip Cancer Wide Excision
Authors: Santoso Boedy Setya , Novastuti Citra Dwi 
Published: February 2020

Foreign objects may be present in the bladder due to deliberate insertion or displacement of the surrounding organs. There have been multiple cases of sharp objects such as nails, hair pins, and screws, as well as large objects such as AAA batteries, toothbrushes, and ballpoint pens found in the urethra and the bladder, which must have been aimed to induce sexual satisfaction associated with mental and psychic disorders. The diagnosis was established by means of radiological examinations, ie thoracic x-ray, KUB, and urethrography. This article reported a 32-year-old man with headset inserted to penile until bladder and could not be pulled out again. The patient complained pain and bleeding out of the urinary tract. We performed vesicotomy and pulling the out headset from bladder. The operation was succesful. In conclusion, the case of a headset in the bladder has been treated successfully with vesicotomy.
CORRELATION BETWEEN THREE COLUMN CONCEPT CLASSIFICATION AND INTERNAL FIXATION PROCEDURE OF TIBIAL PLATEAU PATIENTS AT DR. SOETOMO HOSPITAL
Authors: Utomo Dwikora Novembri , Subiantoro Januar Ari 
Published: February 2020

Background: Tibial Plateau Fracture is one of the most common case seen in orthopaedics and the most classification system used is Schaetzker Classification. This classification is using X ray photograph to classify the fracture and it has limitation to describing a posterior column in tibial plateau fracture since X-ray is a 2D projection. Nowadays surgeon over the world start to using Three Column concept classification because it has a better image of 3D visualization of tibial plateau. Purpose: To know which one classification is more accurate in describing tibial plateau fracture in Dr. Soetomo Hospital period January 2015 until September 2017.Methods: This study is retrospective study, we collected data of patients with Tibial Plateau fracture that has been operated in Dr. Soetomo hospital from January 2015 – September 2017.Results: From the study found 24 patients that match with inclusion criteria. All patients are classified with Schaetzker and Three Column Classification. The most type of fracture based on Schaetzker Classification is Type 2 (7 patients) and based on Three Column Classification is type Three Column (11 patients) and the most action in Three Column type is Internal Fixation with double plate insertion (55 %).Conclusion: Three Column Classification is more accurate to describe type fracture in posterior part than Schaetzker. Three Column Classification is recommended to make easier decision for Tibial Plateau fracture treatment and prevent any loss of correction.
The utility of red cell distribution width to predict mortality of septic patients in a tertiary hospital of Nepal.
Authors: Ghimire Rajan , Shakya Yogendra Man , Shrestha Tirtha Man , Neupane Ram Prasad 
Published: February 2020

Abstract
Background : Sepsis is a common problem encountered in the emergency room which needs to be intervened early. Predicting prognosis is always a difficult task in busy emergency rooms using present scores, which has a number of variables to calculate. Red cell distribution width (RDW) is an easy, cheap, and efficacious score to predict the severity and mortality of patients with sepsis. Method: This prospective analytical study was conducted in the emergency room of Tribhuvan University Teaching Hospital among the patients age ≥16 years and with a clinical diagnosis of sepsis using qSOFA score. 148 patients were analyzed in the study by using a non-probability purposive sampling method. Result: RDW is more efficacious test to predict mortality in sepsis (Area under the Curve of 0.734; 95% C. I= 0.649-0.818; p-value=0.000) than APACHE II (AUC of 0.728; 95% C. I= 0.637 to 0.819; p-value=0.000) or SOFA (AUC of 0.680, 95% C.I =0.591-0.770; p-value=0.001). Youden Index was maximum (37%) at RDW value 14.75, which has a sensitivity of 83% (positive likelihood ratio=1.81) and specificity of 54% (negative likelihood ratio=0.32). Out of 44 patients with septic shock 16 died (36.4 %) and among 104 patients without septic shock, 24 died (22.9%) which had the odds ratio of 0.713 (p=0.555, 95% C. I= 0.231-2.194). Overall mortality was 27.02% (n=40). RDW subgroup analysis showed no mortality in low RDW (<13.1) subgroup, 3.6% mortality in moderate (13.1 to 14) RDW group, 22.0% mortality in high (14 to >15.6) RDW group and 45.9% mortality in very high (>15.6) RDW group. Significant mortality difference was seen in high and very high RDW subgroups with a p-value of 0.003 and 0.008 respectively. Conclusion: RDW can be used as a good prognostic score to predict the mortality of patients with sepsis in the emergency room. RDW is a more efficacious test to predict mortality in sepsis than APACHE II or SOFA scores. Keywords : red cell distribution width, sepsis, emergency care, mortality
Evolution of comorbidities in people living with HIV between 2004 and 2014: Cross-sectional analyses from ANRS CO3 Aquitaine Cohort
Authors: Bonnet Fabrice , Marec Fabien Le , Leleux Olivier , Gerard Yann , Neau Didier , Lazaro Estibaliz , Duffau Pierre , Caubet Olivier , Vandenhende Marrie-Anne , Mercie Patrick , Cazanave Charles , Dabis Francois 
Published: February 2020

Abstract
Background:
The objective of the present study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) included in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management.
Methods:
The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, regarding patient characteristics, HIVRNA and CD4 counts and prevalence of some of the common comorbidities and treatment.
Results:
2,138 PLHIV (71% male, median age 52.2 years in 2014), who had at least one visit registered in the cohort both in 2004 and 2014 were included in the study.
We have observed a significant increase in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin).
This is also reflected in an increase in the proportion of patients in the high or very high risk groups in the different disease risk scores for CKD, CVE and bone fracture score.
Conclusions:
Between 2004 and 2014, the population aged and experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Careful HIV management according to current recommendations, and optimal selection of antiretrovirals, in addition to a good control of risk factors for these comorbidities, through lifestyle improvements and preventative measures, could lead to an early management of these comorbidities and to a continuous improvement of PLHIV health status.
Forecasting incidence of infectious diarrhea using random forest in Jiangsu rovince, China
Authors: Fang Xinyu , Liu Wendong , Ai Jing , He Mike , Wu Ying , Shi Yingying , Shen Wenqi , Bao Changjun 
Published: February 2020

Abstract
Background: Infectious diarrhea can lead to a considerable global disease burden. Thus, the accurate prediction of an infectious diarrhea epidemic is crucial for public health authorities. This study was aimed at developing an optimal random forest (RF) model, considering meteorological factors used to predict an incidence of infectious diarrhea in Jiangsu Province, China. Methods: An RF model was developed and compared with classical autoregressive integrated moving average (ARIMA)/X models. Morbidity and meteorological data from 2012 to 2016 were used to construct the models and the data from 2017 were used for testing. Results: The RF model considered atmospheric pressure, precipitation, relative humidity, and their lagged terms, as well as 1–4 week lag morbidity and time variable as the predictors. Meanwhile, a univariate model ARIMA(1,0,1)(1,0,0) 52 (AIC=−575.92, BIC=−558.14) and a multivariable model ARIMAX(1,0,1)(1,0,0) 52 with 0-1 week lag precipitation (AIC=−578.58, BIC=−578.13) were developed as benchmarks . The RF model outperformed the ARIMA/X models with a mean absolute percentage error (MAPE) of approximately 20% . The performance of the ARIMAX model was comparable to that of the ARIMA model with a MAPE reaching approximately 30%. Conclusions: The RF model fitted the dynamic nature of an infectious diarrhea epidemic well and delivered an ideal prediction accuracy . It comprehensively combined the synchronous and lagged effects of meteorological factors; it also integrated the autocorrelation and seasonality of the morbidity. The RF model can be used to predict the epidemic level and has a high potential for practical implementation.