bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity
Authors: Holmström Tim H. , Moilanen Anu-Maarit , Ikonen Tarja , Björkman Mari L. , Linnanen Tero , Wohlfahrt Gerd , Karlsson Stefan , Oksala Riikka , Korjamo Timo , Samajdar Susanta , Rajagopalan Srinivasan , Chelur Shekar , Narayanan Kishore , Ramachandra Raghuveer K. , Mani Jiju , Nair Rashmi , Gowda Nagaraj , Anthony Thomas , Dhodheri Samiulla , Mukherjee Subhendu , Ujjinamatada Ravi K. , Srinivas Nanduri , Ramachandra Murali , Kallio Pekka J. 
Published: October 2018

Abstract
Alterations in the gene encoding for the FGFR and upregulation of the VEGFR are found often in cancer, which correlate with disease progression and unfavorable survival. In addition, FGFR and VEGFR signaling synergistically promote tumor angiogenesis, and activation of FGFR signaling has been described as functional compensatory angiogenic signal following development of resistance to VEGFR inhibition. Several selective small-molecule FGFR kinase inhibitors are currently in clinical development. ODM-203 is a novel, selective, and equipotent inhibitor of the FGFR and VEGFR families. In this report we show that ODM-203 inhibits FGFR and VEGFR family kinases selectively and with equal potency in the low nanomolar range (IC50 6–35 nmol/L) in biochemical assays. In cellular assays, ODM-203 inhibits VEGFR-induced tube formation (IC50 33 nmol/L) with similar potency as it inhibits proliferation in FGFR-dependent cell lines (IC50 50–150 nmol/L). In vivo, ODM-203 shows strong antitumor activity in both FGFR-dependent xenograft models and in an angiogenic xenograft model at similar well-tolerated doses. In addition, ODM-203 inhibits metastatic tumor growth in a highly angiogenesis-dependent kidney capsule syngenic model. Interestingly, potent antitumor activity in the subcutaneous syngenic model correlated well with immune modulation in the tumor microenvironment as indicated by marked decrease in the expression of immune check points PD-1 and PD-L1 on CD8 T cells and NK cells, and increased activation of CD8 T cells. In summary, ODM-203 shows equipotent activity for both FGFR and VEGFR kinase families and antitumor activity in both FGFR and angigogenesis models.
Показники дерматогліфіки як маркери для побудови математичних моделей ризику виникнення зубощелепних аномалій
Authors: Kazakova R. V. , Melnyk V. S. , Horzov L. F. 
Published: October 2018

Резюме. Дерматогліфічні обстеження широко застосовують у діагностиці багатьох уроджених і набутих захворювань. Доведено, що показники дерматогліфіки можуть бути використані як маркери полігенної системи для дослідження деяких закономірностей фенотипового прояву полігенних систем в онтогенезі. Вивчення спільних зв’язків між пальцевими відбитками і зубощелепними аномаліями може допомогти на ранньому етапі виявити осіб із генетичною схильністю.
Мета дослідження – розробити прогностичні математичні моделі можливості виникнення зубощелепних аномалій у чоловіків і жінок на основі аналізу особливостей дерматогліфічних показників.
Матеріали і методи. Проведено дерматогліфічне дослідження за методикою H. Cummins і Ch. Midlo у 34 чоловіків та у 36 жінок із зубощелепними аномаліями віком 35–44 роки. Як контроль використано результати дерматогліфічних досліджень 43 практично здорових чоловіків і 44 жінок аналогічного віку.
Результати досліджень та їх обговорення. Дискримінантні моделі за допомогою дерматогліфічних показників дозволили розділити міських жителів м. Ужгорода на здорових і хворих із зубощелепними аномаліями. Найбільший внесок у дискримінацію між здоровими і хворими чоловіками має довжина лінії аd на правій кисті, а між здоровими і хворими жінками – наявність осьового трирадіуса t, індексу Каміннса і довжини лінії ct на лівій кисті.
Висновки. Дискримінантні моделі виникнення зубощелепних аномалій, залежно від дерматогліфічних показників, є адекватними і можуть використовуватися для раннього прогнозу ризику виникнення цього захворювання.
Ocupação
Authors: Guedes Ângelo Dimitre Gomes 
Published: October 2018

Uma cidade constitui-se como um território em expansão cujas partes se entrelaçam por inúmeras camadas, veredas e uma multiplicidade de relações entre os corpos que a percorrem, a ocupam e a reconfiguram. Com todo este movimento, as ruas se mostram como vias que permitem transitar no tempo e reunir elementos culturais de diferentes origens e circunstâncias. Isso pode se manifestar com a realização de festas populares cujas tradições são passadas através de gerações. Em Barcelona, no solstício de verão, por exemplo, costuma se celebrar a noite de São João. As ruas tornam-se palco de encontros improváveis: ritos e condutas que exploram múltiplas direções de espaço e de tempo. O presente ensaio[1] mostra uma narrativa visual sobre a ocupação deste território: um jogo de inúmeras potencialidades documentais e ficcionais da imagem fotográfica.
[...] dizem que é possível encontrar mais do que se pode ver nos ritos realizados. Ao anoitecer, algo estranho ocupa as ruas da cidade e manifesta uma misteriosa sonoridade. O aventurar-se por essas ruas durante essas celebrações, revela-se um jogo de potenciais caminhos, encontros, desvios, camadas, misturas e combinações. (GUEDES, 2017, p. 18).

[1] Este ensaio reúne imagens que foram apresentadas em festivais e exposições. Uma das imagens, por exemplo, foi escolhida na Convocatória do Festival de Fotografia de Tiradentes 2017 para compor a Exposição Coletiva “Ficções: a fotografia além do real. Algumas dessas imagens também foram publicadas no catálogo da exposição Arte e Linguagens Contemporâneas realizada no Museu de Imagem e Som (GUEDES, 2017).
Polygenic Contribution in Individuals With Early-Onset Coronary Artery Disease
Authors: Thériault Sébastien , Lali Ricky , Chong Michael , Velianou James L. , Natarajan Madhu K. , Paré Guillaume 
Published: October 2018

Background
Despite evidence of high heritability, monogenic disorders are identified in a minor fraction of individuals with early-onset coronary artery disease (EOCAD). We hypothesized that some individuals with EOCAD carry a high number of common genetic risk variants, with a combined effect similar to Mendelian forms of coronary artery disease, such as familial hypercholesterolemia.

Methods and Results

To confirm the polygenic contribution to EOCAD (age of ≤40 years for men and ≤45 years for women), we calculated in 111 418 British participants from the UK Biobank cohort a genetic risk score (GRS) based on the presence of 182 independent variants associated with coronary artery disease (GRS182). Participants with a diagnosis of EOCAD who underwent a revascularization procedure (n=96) had a significantly higher GRS182 (
P
=3.21×10
−9
) than those without EOCAD. An increase of 1 SD in GRS182 corresponded to an odds ratio of 1.84 (1.52–2.24) for EOCAD. The prevalence of a polygenic contribution that increased EOCAD risk similar to what is observed in heterozygous familial hypercholesterolemia was estimated at 1 in 53. In a local cohort of individuals with EOCAD (n=30), GRS182 was significantly increased compared with UK Biobank controls (
P
=0.001). Seven participants (23%) had a GRS182 corresponding to an estimated 2-fold increase in EOCAD risk; none had a rare mutation involved in monogenic dyslipidemia or EOCAD.

Conclusions
These results suggest a significant polygenic contribution in individuals presenting with EOCAD, which could be more prevalent than familial hypercholesterolemia. Determination of the polygenic risk component could be included in the diagnostic workup of patients with EOCAD.
Impact of a Claims-Based Frailty Indicator on the Prediction of Long-Term Mortality After Transcatheter Aortic Valve Replacement in Medicare Beneficiaries
Authors: Kundi Harun , Valsdottir Linda R. , Popma Jeffrey J. , Cohen David J. , Strom Jordan B. , Pinto Duane S. , Shen Changyu , Yeh Robert W. 
Published: October 2018

Background
Prospectively collected frailty markers are associated with an incremental 1-year mortality risk after transcatheter aortic valve replacement (TAVR) compared with comorbidities alone. Whether information on frailty markers captured retrospectively in administrative billing data is similarly predictive of long-term mortality after TAVR is unknown. We sought to characterize the prognostic importance of frailty factors as identified in healthcare billing records in comparison to validated measures of frailty for the prediction of long-term mortality after TAVR.

Methods and Results

Adult patients undergoing TAVR between August 25, 2011, and September 29, 2015, were identified among Medicare fee-for-service beneficiaries. The Johns Hopkins Claims–based Frailty Indicator was used to identify frail patients. We used nested Cox regression models to identify claims-based predictors of mortality up to 4 years post-procedure. Four groups of variables, including cardiac risk factors, noncardiac risk factors, patient procedural risk factors, and nontraditional markers of frailty, were introduced sequentially, and their integrated discrimination improvement was assessed. A total of 52 338 TAVR patients from 558 clinical sites were identified, with a mean follow-up time period of 16 months. In total, 14 174 (27.1%) patients died within the study period. The mortality rate was 53.9% at 4 years post-TAVR. A total of 34 863 (66.6%) patients were defined as frail. The discrimination of each of the 4 models was 0.60 (95% CI, 0.59–60), 0.65 (95% CI, 0.64–0.65), 0.68 (95% CI, 0.67–0.68), and 0.70 (95% CI, 0.69–0.70), respectively. The addition of nontraditional frailty markers as identified in claims improved mortality prediction above and beyond traditional risk factors (integrated discrimination improvement: 0.019;
P
<0.001).

Conclusions
Risk prediction models that include frailty as identified in claims data can be used to predict long-term mortality risk after TAVR. Linkage to claims data may allow enhanced mortality risk prediction for studies that do not collect information on frailty.
Pharmacological Cardioversion With Antazoline in Atrial Fibrillation: The Results of the CANT Study
Authors: Wybraniec Maciej T. , Wróbel Wojciech , Wilkosz Katarzyna , Wrona Karolina , Bula Karolina , Mizia‐Stec Katarzyna 
Published: October 2018

Background

Antazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrillation with intravenous antazoline (
CANT
[Cardioversion With Antazoline Mesylate] study) in the setting of the emergency department.

Methods and Results

After reviewing 1984 medical records, 450 eligible patients (22.7%) with short‐duration atrial fibrillation subject to pharmacological cardioversion were enrolled in a retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of the attending physician. The primary end point was successful cardioversion in the emergency department. The safety end point comprised bradycardia <45 bpm, hypotension, syncope, or death. The study population (mean age, 65.5±11.9 years; 52.9% females) was characterized by a median atrial fibrillation episode duration of 10 hours. Antazoline, alone or in combination, was administered in 24.2% (n=109) and 40% (n=180), respectively; amiodarone was administered in 46.7% and propafenone in 9.3%, while ≥2 antiarrhythmic drugs were administered in 19.8% of patients. Antazoline had the highest success rate of pharmacological cardioversion among all drugs (85.3%), which was comparable with propafenone (78.6%; relative risk, 1.09, 95% confidence interval, 0.91–1.30;
P
=0.317) and higher than amiodarone treatment (66.7%; relative risk, 1.28, 95% confidence interval, 1.13–1.45;
P
<0.001; number needed to treat, 5.4). The rate of cardioversion with antazoline alone was higher than combined amiodarone and/or propafenone (68.1%; relative risk, 1.25; 95% confidence interval, 1.12–1.40,
P
=0.0001). No safety end points were reported in the antazoline group, while 5 incidents occurred in the non‐antazoline cohort (
P
=0.075).

Conclusions
Antazoline represents an efficacious and safe method of pharmacological cardioversion in a real‐life setting.
Improved Estimation of the Specific Attenuation and Backscatter Differential Phase over Short Rain Paths
Authors: Reinoso-Rondinel Ricardo , Unal Christine , Russchenberg Herman 
Published: October 2018

AbstractIn radar polarimetry, the differential phase consists of the propagation differential phase and the backscatter differential phase . While is commonly used for attenuation correction (i.e., estimation of the specific attenuation A and specific differential phase ), recent studies have demonstrated that can provide information concerning the dominant size of raindrops. However, the estimation of and is not straightforward given their coupled nature and the noisy behavior of , especially over short paths. In this work, the impacts of estimating on the estimation of A over short paths, using the extended version of the ZPHI method, are examined. Special attention is given to the optimization of the parameter α that connects and A. In addition, an improved technique is proposed to compute from and in rain. For these purposes, diverse storm events observed by a polarimetric X-band radar in the Netherlands are used. Statistical analysis based on the minimum errors associated with the optimization of α and the consistency between and A showed that more accurate and stable α and A are obtained if is estimated at range resolution, which is not possible by conventional range filtering techniques. Accurate estimates were able to depict the spatial variability of dominant raindrop size in the observed storms. By following the presented study, the ZPHI method and its variations can be employed without the need for considering long paths, leading to localized and accurate estimation of A and .
Intraductal Pneumatic Lithotripsy after Extended Transoral Duct Surgery in Submandibular Sialolithiasis
Authors: Koch Michael , Schapher Mirco , Mantsopoulos Konstantinos , Goncalves Miguel , Iro Heinrich 
Published: October 2018

ObjectivePersistent, residual, or recurrent stones after transoral duct surgery are always associated with hilar to intraparenchymal and/or multiple sialolithiasis, causing difficulties in the treatment. This study was performed to assess the value of intraductal lithotripsy in the treatment of persistent, residual, or recurrent sialolithiasis after extended duct surgery in the submandibular gland.Study DesignRetrospective study covering February 2015 to June 2018.Study SettingTertiary referral center for salivary gland diseases.Subjects and MethodsAfter extended ductal surgery, 39 patients presenting with persistent, residual, or recurrent stones were treated. Four patients had persistent stones; 16 had residual stones; and 19 presented with recurrent stones. Among these patients, 50 stones were treated with intraductal pneumatic lithotripsy. Fragmentation rate, stone‐free rate, and symptom‐free rate after treatment with intraductal lithotripsy were outcome measures.ResultsOf the 39 patients, 97.4% became stone‐free, and all were symptom‐free. Ninety‐eight percent of the stones were completely fragmented. For 23.1% of the patients, >1 stone was treated with intraductal lithotripsy. All patients with persistent stones, 93.7% of those with residual stones, and all with recurrent stones became stone‐free and symptom‐free. No severe complications developed.ConclusionsThis study shows that patients presenting with difficult and/or multiple sialolithiasis after extended transoral submandibular duct surgery can be treated with success rates >97%. For multiple sialolithiasis in particular, a multimodal treatment approach with interventional sialendoscopy and intraductal lithotripsy as a central element is a prerequisite for success, as this enables the most difficult part to be performed with high success rates.
Analysis of the risk factors for contrast-induced nephropathy in over-aged patients receiving coronary intervention
Authors: Pan Hui-Chao , Wu Xian-Hao , Wan Qian-Li , Liu and Bao-Hong , Wu Xu-Sheng 
Published: October 2018

Contrast-induced nephropathy has been the common cause of hospital-acquired acute kidney injury in the elderly patients. This study aimed to analyze the risk factors for contrast-induced nephropathy in over-aged patients undergoing coronary angiography or percutaneous coronary intervention. A total of 470 over-aged patients (≥80 years old) were judged as the contrast-induced nephropathy group ( n = 46) and non-contrast-induced nephropathy group ( n = 424) according to the postoperative 48-h serum creatinine levels. The patients’ clinical information such as hypertension grade, number and degree of coronary artery stenosis, and death rate was compared. The risk factors for contrast-induced nephropathy were also analyzed. The hypertension grade in the contrast-induced nephropathy group was significantly higher than that in the non-contrast-induced nephropathy group ( P = 0.004). The degree of coronary artery stenosis was significantly more in the contrast-induced nephropathy group compared with the non-contrast-induced nephropathy group ( P = 0.003). The death rate of the contrast-induced nephropathy group (15.8%) was significantly higher than that of the non-contrast-induced nephropathy group (0.6%; P = 0.000). The percentage of patients with abnormal urine microalbumin was significantly bigger in the contrast-induced nephropathy group (62.5%) when comparing to the non-contrast-induced nephropathy group (23.6%; P = 0.00). Besides, there was also significant difference in the emergency/selective operation between the contrast-induced nephropathy group and non-contrast-induced nephropathy group ( P = 0.001). Further, hypertension grade ( P = 0.019), emergency/selective operation ( P = 0.025), degree of coronary artery stenosis ( P = 0.038), eGFR ( P = 0.034), and urine microalbumin ( P = 0.005) were the risk factors for contrast-induced nephropathy. Hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for contrast-induced nephropathy in over-aged patients receiving coronary angiography and percutaneous coronary intervention, providing guidance for the clinical prevention of contrast-induced nephropathy.Impact statementIn this work, we evaluated the risk factors for contrast-induced nephropathy (CIN) in over-aged patients receiving coronary angiography (CAG) and percutaneous coronary intervention (PCI). We found that hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for CIN in over-aged patients receiving CAG and PCI. This study provides guidance for the clinical prevention of CIN in over-aged patients undergoing coronary intervention, highlighting that a perioperative comprehensive management strategy is needed to improve the prognosis.
Bayesian Adaptive Design for Finding the Maximum Tolerated Sequence of Doses in Multicycle Dose-Finding Clinical Trials
Authors: Lyu Jiaying , Curran Emily , Ji Yuan 
Published: October 2018

Purpose Statistical designs for traditional phase I dose-finding trials consider dose-limiting toxicity in the first cycle of treatment. In reality, patients often go through multiple cycles of treatment and may experience toxicity events in more than one cycle. Therefore, it is desirable to identify the maximum tolerated sequence of three doses across three cycles of treatment. Methods Motivated by a three-cycle dose-finding clinical trial for a rare cancer with a JAK inhibitor, we proposed and implemented a simple Bayesian adaptive dose-cycle finding (BaSyc) design that allows intercycle and intrapatient dose modification. Because of the patient-specific dosing strategy over cycles, the BaSyc design is suited as a method in precision oncology. Results BaSyc is simple and transparent because its algorithm can be summarized as two tabulated decision rules before the trial starts, allowing physicians to visually examine these rules. In addition, BaSyc employs a time-saving enrollment scheme that speeds up the trial. Extensive simulation studies show that BaSyc has desirable operating characteristics in identifying the maximum tolerated sequence. Conclusion The BaSyc design provides a first-of-kind multicycle approach for dose finding and will likely lead to better and safer patient care and drug development.
Mild Perioperative Hypothermia and Myocardial Injury: A Retrospective Cohort Analysis
Authors: Schacham Yehoshua N. , Cohen Barak , Bajracharya Gausan R. , Walters Michael , Zimmerman Nicole , Mao Guangmei , Tanios Marianne A. , Sessler Daniel I. 
Published: October 2018

BACKGROUND:
We tested the primary hypothesis that final intraoperative esophageal temperature is associated with increased odds of a composite of in-hospital all-cause mortality and myocardial injury within 7 days after noncardiac surgery. Secondary exposures were time-weighted average intraoperative temperature and area <37°C threshold.

METHODS:
Myocardial injury was defined by postoperative fourth-generation troponin T ≥0.03 ng/mL apparently due to cardiac ischemia. Data were extracted for inpatients who had noncardiac surgery with general anesthesia at the Cleveland Clinic between 2012 and 2015. All had esophageal temperature monitoring and routine postoperative troponin monitoring. We estimated the confounder-adjusted association between final intraoperative esophageal temperature and the collapsed composite with multivariable logistic regression. We similarly estimated associations with time-weighted average intraoperative temperature and area <37°C.

RESULTS:
Two thousand two hundred ten patients were included. Nearly all final esophageal temperatures were 36°C–37°C. Ninety-seven patients (4.4%) had myocardial injury, and 7 (0.3%) died before discharge. Final intraoperative core temperature was not associated with the collapsed composite: odds ratio, 0.91 (95% confidence interval, 0.68–1.24) per 1°C decrease. Similarly, neither of the secondary exposures was associated with the composite outcome.

CONCLUSIONS:
We did not observe an association between mild perioperative hypothermia and mortality or myocardial injury in adults having noncardiac surgery. However, the range of final intraoperative temperatures was small and largely restricted to the normothermic range (36°C–37°C). Trials are needed to further assess the effect of temperature on myocardial injury.
Dreaming Transnationally in America
Authors: Poblete Juan 
Published: October 2018

Abstract
Transnational circuits, as social practices, are not immaterial or virtual, but they do not depend on traditional understandings of one territorial location. Rather than fully and singularly determining the lives of its inhabitants, these local spaces belong now to a transterritory established by the physical, cultural, and imaginative labor of migrants connecting two such spaces, beyond the boundaries of one nation-state. Transnationalism, as a field of studies, has focused on these dynamics. Here they are used to address the question of a possible transnational politics inside the United States, connecting the lives of those who have the most and those who have the least, whether they are US nationals or foreign immigrants.
Paper Trails
Authors: Sartorius David 
Published: October 2018

Abstract
This essay reflects on the materiality of migration with a focus on passports and other kinds of documentary permissions for travel. It argues that throughout the history of the Americas passports have acquired meanings exceeding contemporary associations with national citizenship that are discernible in literary works and in the archival record. It looks to documentary practices in Latin America and the Caribbean to decenter the United States from studies of border crossing and Latinx subjectivities, suggesting intersecting hemispheric practices that delineate the relative importance of being documented or undocumented.