bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the nature of the microwave field emerging from a composite pupil
Authors: Cacciari Ilaria , Mugnai Daniela , Ranfagni Anedio 
Published: June 2020

Further experimental investigations in the microwave field emerging from a composite pupil are reported in order to determine the nature of the wave propagation. The experiments consisted of delay-time measurements as a function of the distance of the detector from the pupil under test, as well as of the phase variation of a radio-frequency signal at 35 MHz that modulated the same microwave carrier at 9.33 GHz. In addition, measurements employing an admittance comparator were made in order to determine the character of the propagation impedance. All results obtained confirmed superluminal behavior in the near field, up to a distance of about 40 cm. These results were then interpreted within the framework of a stochastic model.
Tunable wavelength conversion based on a nanoscale slot waveguide in communication bands
Authors: Guo Rujing , Han Mengxiong , Wei Peiqi , Yin Shenwei , Ma Yan 
Published: June 2020

This paper introduces a new nanoscale slot waveguide using organic material, graphene, and silicon-based materials. The physical mechanism of additional biased voltage can improve the performance of graphene-related waveguide, the proposed waveguide exhibits tunable performance including effective refractive index and dispersion without changing its structure and geometric dimension, which contributes to the practical value in future complex signal processing system. Based on the waveguide, wavelength conversion based on four-wave mixing is theoretically investigated in the near-infrared region and the tunable wavelength conversion is realized. These research results will have potential in the fields of data transmission and optical communications and help researchers deeply understand the physical mechanisms and nonlinear effects about the optical pulse generation processes and signal processing.
Tracking the Flu Virus in a Room Mechanical Ventilation Using CFD Tools and Effective Disinfection of an HVAC System
Authors: Hasan Ali 
Published: June 2020

Recent concerns raised by the World Health Organization over the Coronavirus raised a worldwide reaction. Governments are racing to contain and stop the Coronavirus from reaching an epidemic/pandemic status. This research presents a way in tracking such a virus or any contagious germ capable of transferring through air specifically where such a transfer can be assisted by a mechanical room ventilation system. Tracking the spread of such a virus is a complicated process, as they can exist in a variety of forms, shapes, sizes, and can change with time. However, a beginning has to be made at some point. Assumptions had to be made based on published scientific data, and standards. The tracking of airborne viruses was carried out on the following assumption (for illustrative purposes); one person with one sneeze in a period of 600 s. The presence of viruses was tracked with curves plotted indicating how long it could take to remove the sneezed viruses from the mechanically ventilated room space. Results gave an indication of what time span is required to remove airborne viruses. Thus, we propose the following: (a) utilizing CFD software as a possible tool in optimizing a mechanical ventilation system in removing contagious viruses. This will track the dispersion of viruses and their removal. The numerical solution revealed that with one typical adult human sneeze, it can take approximately 640 s to reduce an average sneeze of 20,000 droplets to a fifth; (b) upscaling the status of human comfort to a “must have” with regards to the 50% relative humidity, and the use of Ultraviolet germicidal irradiation (UVGI) air disinfection in an epidemic/pandemic condition. A recommendation can be presented to the local authorities of jurisdiction in enforcing the above proposals partially/fully as seen fit as “prevention is better than cure”. This will preclude the spread of highly infectious viruses in mechanically ventilated buildings.
p38γ MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis
Authors: Wang Fang , Qi Xiao-Mei , Wertz Ryan , Mortensen Matthew , Hagen Catherine , Evans John , Sheinin Yuri , James Michael , Liu Pengyuan , Tsai Susan , Thomas James , Mackinnon Alexander , Dwinell Michael , Myers Charles R. , Bartrons Bach Ramon , Fu Liwu , Chen Guan 
Published: June 2020

Abstract

KRAS is mutated in most pancreatic ductal adenocarcinomas (PDAC) and yet remains undruggable. Here, we report that p38γ MAPK, which promotes PDAC tumorigenesis by linking KRAS signaling and aerobic glycolysis (also called the Warburg effect), is a novel therapeutic target. p38γ interacted with a glycolytic activator PFKFB3 that was dependent on mutated KRAS. KRAS transformation and overexpression of p38γ increased expression of PFKFB3 and glucose transporter GLUT2, conversely, silencing mutant KRAS, and p38γ decreased PFKFB3 and GLUT2 expression. p38γ phosphorylated PFKFB3 at S467, stabilized PFKFB3, and promoted their interaction with GLUT2. Pancreatic knockout of p38γ decreased p-PFKFB3/PFKFB3/GLUT2 protein levels, reduced aerobic glycolysis, and inhibited PDAC tumorigenesis in KPC mice. PFKFB3 and GLUT2 depended on p38γ to stimulate glycolysis and PDAC growth and p38γ required PFKFB3/S467 to promote these activities. A p38γ inhibitor cooperated with a PFKFB3 inhibitor to blunt aerobic glycolysis and PDAC growth, which was dependent on p38γ. Moreover, overexpression of p38γ, p-PFKFB3, PFKFB3, and GLUT2 in PDAC predicted poor clinical prognosis. These results indicate that p38γ links KRAS oncogene signaling and aerobic glycolysis to promote pancreatic tumorigenesis through PFKFB3 and GLUT2, and that p38γ and PFKFB3 may be targeted for therapeutic intervention in PDAC.

Significance:
These findings show that p38γ links KRAS oncogene signaling and the Warburg effect through PFKBF3 and Glut2 to promote pancreatic tumorigenesis, which can be disrupted via inhibition of p38γ and PFKFB3.
FIP200 Suppresses Immune Checkpoint Therapy Responses in Breast Cancers by Limiting AZI2/TBK1/IRF Signaling Independent of Its Canonical Autophagy Function
Authors: Okamoto Takako , Yeo Syn Kok , Hao Mingang , Copley Mary Rose , Haas Michael A. , Chen Song , Guan Jun-Lin 
Published: June 2020

AbstractImmune checkpoint inhibitors (ICI) have the potential to induce durable therapeutic responses, yet response rates in breast cancer are modest and limited to particular subtypes. To expand the applicability of ICI, we examined the role of an essential autophagy gene, FIP200, which has been shown to be important for tumor progression in mammary tumors. Specific disruption of the autophagy function of FIP200 or complete ablation of FIP200 in genetic mouse models revealed that FIP200 autophagy function was required for progression of PyMT-driven mammary tumors. However, a noncanonical autophagy function of FIP200 was responsible for limiting T-cell recruitment and activation of the TBK1-IFN signaling axis. FIP200 also interacted with the TBK1 adaptor protein, AZI2, which was crucial for activation of TBK1 following FIP200 ablation. Accordingly, disrupting the noncanonical autophagy function of FIP200 in combination with ICI therapy led to superior, durable responses in immune-competent models of breast cancer. Collectively, these insights could guide future development of therapeutic agents against FIP200 for combinatorial ICI therapies in nonresponsive breast cancers.Significance:These findings show that deletion of FIP200 enhances immune checkpoint inhibitor efficacy in nonresponsive breast cancer.
R-spondin2 Suppresses the Progression of Hepatocellular Carcinoma via MAPK Signaling Pathway
Authors: Zheng Chang , Zhou Fan , Shi Liang Liang , Xu Gui Fang , Zhang Bin , Wang Lei , Zhuge Yuzheng , Zou Xiao Ping , Wang Yi 
Published: June 2020

Abstract

The R-spondin family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established R-spondin2–overexpressing and knockdown cell lines and measured their viabilities and invasion abilities in vitro and their oncogenic capacity in vivo. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between R-spondin2–overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, in vivo experiments indicated that R-spondin2 knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the R-spondin2, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway.

Implications:
R-spondin2 gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.
Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial
Authors: Hurwitz Lauren M. , Kulac Ibrahim , Gumuskaya Berrak , Valle Javier A. Baena Del , Benedetti Ines , Pan Fan , Liu Jun O. , Marrone Michael T. , Arnold Kathryn B. , Goodman Phyllis J. , Tangen Catherine M. , Lucia M. Scott , Thompson Ian M. , Drake Charles G. , Isaacs William B. , Nelson William G. , De Marzo Angelo M. , Platz Elizabeth A. 
Published: June 2020

Abstract
Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16–27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81–3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk.
РЕЗУЛЬТАТИ ТЕСТУВАННЯ НА БІОМАРКЕР ТУБЕРКУЛЬОЗУ ЛІПОАРАБІНОМАННАН (LAM) У ПАЦІЄНТІВ ТУБЕРКУЛЬОЗНОГО СТАЦІОНАРУ
Authors: Savula М. M. , Vasylyshyn O. V. 
Published: June 2020

Мета роботи – з’ясувати доцільність визначення LAM-антигену в сечі для діагностики туберкульозу.
Матеріали і методи. LAM-антиген в сечі визначали шляхом застосування тесту Aleve Determine TB LAM Ag, рекомендованого для діагностики туберкульозу серед ВІЛ-позитивних осіб. Обстежено 88 дорослих пацієнтів. Активний туберкульоз був у 77 хворих, із них у 73 туберкульоз легень (у 6 в поєднанні з ВІЛ-інфекцією і у 67 ВІЛ-негативних).
Результати та обговорення. Позитивні результати LAM-тесту отримані в 11 із 77 (14,3 %) хворих із активним туберкульозом, всі 11 – серед 73 (15,1 %) осіб з туберкульозом легень. LAM-антиген виявлено у 4 із 6 ВІЛ-інфікованих осіб і у 7 з 67 (10,4 %) ВІЛ-негативних. У двох ВІЛ-інфікованих жінок виявлення LAM-антигену було єдиним етіологічним підтвердженням активного туберкульозу за негативних результатів мікроскопічних і молекулярно-генетичного досліджень.
У всіх 7 ВІЛ-негативних осіб з позитивними результатами LAM-тесту були тяжкі поширені форми легеневого туберкульозу і супровідні хвороби, які могли спричинити пригнічення імунітету.
Висновки. Через низьку чутливість, в наших умовах визначення LAM-антигену в сечі доцільне в окремих випадках у ВІЛ-позитивних осіб, в яких не отримано етіологічного підтвердження туберкульозу іншими методами. Зроблено припущення, що чутливість LAM-тесту може зростати при імунодефіцитних станах, спричинених, крім ВІЛ-інфекції, також іншими чинниками.
ЛАЙМ-БОРЕЛІОЗ У ДІТЕЙ
Authors: Nykytyuk S. O. , Klymniuk S. I. 
Published: June 2020

В останні роки значна увага дослідників присвячена проблемам поширення захворюваності на Лайм-бореліоз і вчасної діагностики цього захворювання, зокрема у дітей. Така проблема особливо актуальна в нашій країн, оскільки за 10 років захворюваність на хворобу Лайма зросла в 27 разів.
Основна частина. На підставі ретельного і глибокого аналізу літератури в статті розглядаються проблеми діагностування хвороби Лайма, спричиненої збудниками, які потрапляють в організм унаслідок укусу інфікованих кліщів. У дітей і дорослих тривалий анамнез цих захворювань призводить до тяжких, часом незворотних наслідків. Вони можуть бути пов’язані з неадекватним і несвоєчасним встановленням діагнозу, що є серйозною проблемою, над вирішенням якої працюють учені багатьох країн світу.
Висновок. Хвороба Лайма – це ендемічне захворювання, що набуває характеру пандемії, тому що число хворих на Лайм-бореліоз зростає. Імунітет проти Borrelia burgdorferi не довічний, і у частини людей, що перенесли Лайм-бореліоз (ЛБ), через деякий час можливе повторне зараження. Емпіричне лікування може знизити імунну відповідь, що призведе до помилково негативних результатів серологічних тестів.
СОЦІАЛЬНА, МЕДИЧНА ТА ЕКОНОМІЧНА ЕФЕКТИВНОСТІ ОХОРОНИ ЗДОРОВ’Я В ПЕРІОД ЇЇ РЕФОРМУВАННЯ
Authors: Holiachenko А. O. , Smirnova V. L. , Panchyshyn N. Ya. , Holiachenko O. A. 
Published: June 2020

За 28 років незалежності України на чолі охорони здоров’я стояло 28 міністрів – академіків зі світовим ім’ям, професорів та просто звичайних людей. Усі вони обіцяли поліпшити охорону здоров’я та досягти позитивних наслідків в показниках здоров’я людності. Натомість здоров’я населення невпинно погіршувалося і досягло небачених результатів – зменшення на 8 млн осіб.
Мета дослідження – проаналізувати і оцінити соціальну, медичну та економічну ефективності охорони здоров’я в період її реформування.
Матеріали і методи. Використано дані загальної та галузевої медичної статистики за весь період існування самостійної України, дані соціологічного опитування жінок дітородного віку. Для обробки матеріалів застосовували статистичний, соціологічний методи та системний аналіз.
Результати. На сьогодні відмічено вкрай негативні наслідки в галузях соціальної, медичної та економічної ефективностей охорони здоров’я. Зростає смертність населення, захворюваність, а витрати на медицину залишаються на вкрай низькому рівні. Медична реформа стоїть ніби осторонь від усіх проблем.
Висновки. Медична реформа не вирішує свого основного завдання – забезпечення соціальної, медичної та економічної ефективностей. Продовження цієї традиції призведе до катастрофічних наслідків для українського народу.
Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1‐Year Follow‐Up: Results From WISE‐CVD
Authors: Quesada Odayme , Hermel Melody , Suppogu Nissi , Aldiwani Haider , Shufelt Chrisandra , Mehta Puja K. , Cook‐Wiens Galen , Maughan Jenna , Berman Daniel S. , Thomson Louise E. J. , Handberg Eileen M. , Pepine Carl J. , Bairey Merz C. Noel , Wei Janet 
Published: June 2020

Background
Women with ischemia and no obstructive coronary artery disease are increasingly recognized and found to be at risk for major adverse cardiovascular events.

Methods and Results

In 214 women with suspected ischemia and no obstructive coronary artery disease who completed baseline and 1‐year follow‐up vasodilatory stress cardiac magnetic resonance imaging, we investigated temporal trends in angina (Seattle Angina Questionnaire [SAQ]), myocardial perfusion reserve index, blood pressure, and left ventricular (LV) remodeling and function from baseline to 1‐year follow‐up and explored associations between these different parameters. We observed concordant positive trends in 4/5 SAQ domains, SAQ‐7, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to‐volume ratio. There was no association between SAQ‐7 improvement and myocardial perfusion reserve index improvement over 1‐year follow‐up (
P
=0.1). Higher indexed LV end‐diastolic volume and time to peak filling rate at baseline were associated with increased odds of clinically relevant SAQ‐7 improvement (odds ratio [OR], 1.05; 95% CI, 1.0–1.1; and OR, 2.40; 95% CI, 1.1–5.0, respectively). Hypertension was associated with decreased odds of SAQ‐7 improvement (OR, 0.41; 95% CI, 0.19–0.91).

Conclusions
In women with ischemia and no obstructive coronary artery disease clinically treated with cardiac medications over 1 year, we observed concurrent temporal trends toward improvement in SAQ, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to volume ratio. We showed that abnormalities in LV morphology and diastolic function at baseline were predictive of clinically significant improvement in angina at follow‐up, whereas history of hypertension was associated with lower odds. Future studies are needed to assess the mechanisms and treatments responsible for the improvements we observed.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT02582021.
Healthy Lifestyle for Prevention of Premature Death Among Users and Nonusers of Common Preventive Medications: A Prospective Study in 2 US Cohorts
Authors: Wang Kai , Li Yanping , Liu Gang , Rimm Eric , Chan Andrew T. , Giovannucci Edward L. , Song Mingyang 
Published: June 2020

Background
It remains unknown whether individuals who regularly use preventive medications receive the same benefit from healthy lifestyle as those who do not use medications. We aimed to examine the associations of healthy lifestyle with mortality according to use of major preventive medications, including aspirin, antihypertensives, and lipid‐lowering medications.

Methods and Results

Among 79 043 women in the Nurses' Health Study (1988–2014) and 39 544 men in the Health Professionals Follow‐up Study (1986–2014), we defined a healthy lifestyle score based on body mass index, smoking, physical activity, diet, and alcohol intake. We estimated multivariable hazard ratios (HRs) and population‐attributable risks of death from any cause, cardiovascular disease, cancer, and other causes in relation to healthy lifestyle according to medication use. We documented 35 195 deaths. A similar association of healthy lifestyle score with lower all‐cause mortality was observed among medication users (HR, 0.82 per unit increment; 95% CI, 0.81–0.82) and nonusers (HR, 0.81; 95% CI, 0.79–0.83) (
P
interaction=0.54). The fraction of premature deaths that might be prevented by adherence to the 5 healthy lifestyle factors among medication users and nonusers was 38% (95% CI, 32%–42%) and 40% (95% CI, 29%–50%) for all‐cause mortality, 37% (95% CI, 27%–46%) and 45% (95% CI, 18%–66%) for cardiovascular disease mortality, and 38% (95% CI, 28%–46%) and 33% (95% CI, 14%–49%) for cancer mortality, respectively.

Conclusions
Adherence to a healthy lifestyle confers substantial benefit for prevention of premature death among both regular users and nonusers of preventive medications. Adherence to a healthy lifestyle remains important even among individuals regularly using preventive medications.
Use of QT Prolonging Medications by Hemodialysis Patients and Individuals Without End‐Stage Kidney Disease
Authors: Assimon Magdalene M. , Wang Lily , Pun Patrick H. , Winkelmayer Wolfgang C. , Flythe Jennifer E. 
Published: June 2020

Background
The rate of sudden cardiac death in the hemodialysis population exceeds that of the general population by >20‐fold. Hemodialysis patients may be particularly susceptible to sudden cardiac death provoked by drug‐induced QT prolongation because of their substantial cardiovascular disease burden, exposure to electrolyte shifts during dialysis, and extensive polypharmacy. However, population‐specific data regarding the frequency and patterns of QT prolonging medication use are limited.

Methods and Results
We conducted a descriptive drug utilization study using 3 administrative databases, the United States Renal Data System, MarketScan, and Medicare claims. We characterized the extent and patterns of QT prolonging medication use by adult hemodialysis patients and individuals without end‐stage kidney disease annually from 2012 to 2016. We also identified instances of high‐risk QT prolonging medication use among hemodialysis patients. In total, 338 515 hemodialysis patients and 40.7 million individuals without end‐stage kidney disease were studied. Annual utilization rates of QT prolonging medications with known torsades de pointes risk in hemodialysis patients were ~1.4 to ~2.5 times higher than utilization rates in individuals without end‐stage kidney disease. Hemodialysis patients with demographic and clinical risk factors for drug‐induced QT prolongation were exposed to medications with known torsades de pointes risk more often than patients without risk factors.

Conclusions
Hemodialysis patients use QT prolonging medications with known torsades de pointes risk more extensively than individuals without end‐stage kidney disease. Given the widespread use and instances of high‐risk prescribing, future studies evaluating the cardiac safety of these drugs in the hemodialysis population are needed.