bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer
Authors: Yang Rongqiang , Li Steven W , Chen Zirong , Zhou Xin , Ni Wei , Fu Dongtao A , Lu Jianrong , Kaye Frederic J , Wu Lizi 
Published: August 2018

Abstract

Background
The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets. Here we investigated the role of INSL4, a member of the insulin/IGF/relaxin superfamily, in LKB1-inactivated NSCLCs.

Methods
INSL4 expression was analyzed using global transcriptome profiling, quantitative reverse transcription PCR, western blotting, enzyme-linked immunosorbent assay, and RNA in situ hybridization in human NSCLC cell lines and tumor specimens. INSL4 gene expression and clinical data from The Cancer Genome Atlas lung adenocarcinomas (n = 515) were analyzed using log-rank and Fisher exact tests. INSL4 functions were studied using short hairpin RNA (shRNA) knockdown, overexpression, transcriptome profiling, cell growth, and survival assays in vitro and in vivo. All statistical tests were two-sided.

Results
INSL4 was identified as a novel downstream target of LKB1 deficiency and its expression was induced through aberrant CRTC-CREB activation. INSL4 was highly induced in LKB1-deficient NSCLC cells (up to 543-fold) and 9 of 41 primary tumors, although undetectable in all normal tissues except the placenta. Lung adenocarcinomas from The Cancer Genome Atlas with high and low INSL4 expression (with the top 10th percentile as cutoff) showed statistically significant differences for advanced tumor stage (P < .001), lymph node metastasis (P = .001), and tumor size (P = .01). The INSL4-high group showed worse survival than the INSL4-low group (P < .001). Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated NSCLC cells in vitro and in a mouse xenograft model (n = 5 mice per group). Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival.

Conclusions
LKB1 deficiency induces an autocrine INSL4 signaling that critically supports the growth and survival of lung cancer cells. Therefore, aberrant INSL4 signaling is a promising therapeutic target for LKB1-deficient lung cancers.
Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study
Authors: Kitchlu Abhijat , McArthur Eric , Amir Eitan , Booth Christopher M , Sutradhar Rinku , Majeed Habeeb , Nash Danielle M , Silver Samuel A , Garg Amit X , Chan Christopher T , Kim S Joseph , Wald Ron 
Published: August 2018

Abstract

Background
Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment.

Methods
We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007–2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence.

Results
We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014.

Conclusion
Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.
Unusual polarimetric properties of (101955) Bennu: similarities with F-class asteroids and cometary bodies
Authors: Cellino A , Bagnulo S , Belskaya I N , Christou A A 
Published: August 2018

ABSTRACT
We have obtained polarimetric measurements of asteroid (101955) Bennu, a presumably primitive near-Earth object (NEO) that is the target of NASA’s sample return mission OSIRIS-REx. During our observing campaign, Bennu was visible from Earth under a wide range of illumination conditions, with phase angle in the range 16°–57°. Together with (3200) Phaethon and (152679) 1998 KU2, observed very recently, Bennu is the only existing example of a primitive NEO observed in polarimetric mode over a wide interval of phase angles. Based on our polarimetric data, we propose that Bennu belongs to the unusual F taxonomic class defined in the 80s. According to previous works, the F-class includes objects with cometary features. This fact can be of great importance for the interpretation of the results of the exploration of this object by OSIRIS-REx. From polarimetry we also derive an estimate of the geometric albedo of Bennu: pR = 0.059 ± 0.003.
Functional features defining the efficacy of cholesterol-conjugated, self-deliverable, chemically modified siRNAs
Authors: Shmushkovich Taisia , Monopoli Kathryn R , Homsy Diana , Leyfer Dmitriy , Betancur-Boissel Monica , Khvorova Anastasia , Wolfson Alexey D 
Published: August 2018

Abstract
Progress in oligonucleotide chemistry has produced a shift in the nature of siRNA used, from formulated, minimally modified siRNAs, to unformulated, heavily modified siRNA conjugates. The introduction of extensive chemical modifications is essential for conjugate-mediated delivery. Modifications have a significant impact on siRNA efficacy through interference with recognition and processing by RNAi enzymatic machinery, severely restricting the sequence space available for siRNA design. Many algorithms available publicly can successfully predict the activity of non-modified siRNAs, but the efficiency of the algorithms for designing heavily modified siRNAs has never been systematically evaluated experimentally. Here we screened 356 cholesterol-conjugated siRNAs with extensive modifications and developed a linear regression-based algorithm that effectively predicts siRNA activity using two independent datasets. We further demonstrate that predictive determinants for modified and non-modified siRNAs differ substantially. The algorithm developed from the non-modified siRNAs dataset has no predictive power for modified siRNAs and vice versa. In the context of heavily modified siRNAs, the introduction of chemical asymmetry fully eliminates the requirement for thermodynamic bias, the major determinant for non-modified siRNA efficacy. Finally, we demonstrate that in addition to the sequence of the target site, the accessibility of the neighboring 3′ region significantly contributes to siRNA efficacy.
Prevalence of atheromatous and non-atheromatous cardiovascular disease by age in chronic kidney disease
Authors: Villain Cédric , Metzger Marie , Combe Christian , Fouque Denis , Frimat Luc , Jacquelinet Christian , Laville Maurice , Briançon Serge , Klein Julie , Schanstra Joost P , Robinson Bruce M , Mansencal Nicolas , Stengel Bénédicte , Massy Ziad A 
Published: August 2018

Abstract

Background
Although chronic kidney disease (CKD) and age are major risk factors for cardiovascular disease (CVD), little is known about the relative proportions of atheromatous and non-atheromatous CVD by age in CKD patients.

Methods
We used baseline data from the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort of 3033 patients (65% men) with CKD Stages 3–4 to study crude and adjusted associations between age, the estimated glomerular filtration rate (eGFR), atheromatous CVD (coronary artery disease, peripheral artery disease and stroke) and non-atheromatous CVD (heart failure, cardiac arrhythmia and valvular heart disease).

Results
Mean age was 66.8 and mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR was 32.9 mL/min/1.73 m2. In the &lt;65, (65–74), (75–84) and ≥85 year age groups, the prevalence was, respectively, 18.7, 35.5, 42.9 and 37.8% for atheromatous CVD, and 14.9, 28.4, 38.1 and 56.4% for non-atheromatous CVD. After adjusting for albuminuria, sex and CVD risk factors, the odds ratio (OR) [95% confidence interval (CI)] for (65–74), (75–84) and ≥85 age groups (compared with the &lt;65 group) was, respectively, 1.99 (1.61–2.46), 2.89 (2.30–3.62), 2.72 (1.77–4.18) for atheromatous CVD and 2.07 (1.66–2.58), 3.15 (2.50–3.97), 7.04 (4.67–10.61) for non-atheromatous CVD. Compared with patients with an eGFR ≥30 mL/min/1.73 m2, those with an eGFR &lt;30 mL/min/1.73 m2 had a higher OR for atheromatous CVD [1.21 (1.01–1.44)] and non-atheromatous CVD [1.16 (0.97–1.38)].

Conclusions
In this large cohort of CKD patients, both atheromatous and non-atheromatous CVD were highly prevalent and more frequent in older patients. In a given age group, the prevalence of atheromatous and non-atheromatous CVD was similar (except for a greater prevalence of non-atheromatous CVD after 85).
MODIFICATION INDUCED BY PROTON IRRADIATION IN BAYFOL UV1 7-2 NUCLEAR TRACK DETECTOR
Authors: Nouh S A , Gaballah N , Abou Elfadl A , Alsharif S A 
Published: August 2018

Abstract
Bayfol is a class of polymeric solid state nuclear track detector which has many applications in various radiation detection fields. It is a Makrofol polycarbonate/polyester blend. Samples from Bayfol film have been irradiated with different fluences (1011−1014 p/cm2) of 1 MeV protons at the University of Surrey Ion Beam Center, UK. The resultant effect of proton irradiation on the structural and optical properties of the Bayfol samples has been investigated using X-ray diffraction, Fourier Transform Infrared and UV spectroscopy. The optical energy gap was decreased from 4.24 to 4.03 eV with increasing the proton fluence from 1011 to 1013 p/cm2, and was accompanied by an increase in the Urbach energy from 0.79 to 1.29 eV. This could be correlated to the results obtained from XRD and FTIR spectroscopy. Further, the non-irradiated Bayfol is nearly colorless. It showed significant sensitivity to color by proton irradiation, associated with an increase in the red and yellow color components. The variation of optical and color parameters with the proton fluence indicate that the dynamic range of Bayfol UV1 7-2 is in the fluence range from 1011 to 1013 p/cm2.
Is social investment inimical to the poor?
Authors: Noël Alain 
Published: August 2018

AbstractIn the last two decades, the social investment strategy has been the main approach to welfare state reform. Concretely, two spending programs have dominated the agenda: the expansion of active labor market programs and the development of childcare services. Many authors have suspected, however, that these social investments were realized at the expense of income protection for the poor. This article assesses this potential trade-off with time-series cross-sectional models of the determinants of active labor market policies expenditures, childcare spending and the adequacy of minimum income protection (MIP), for 18 OECD countries between 1990 and 2009. It turns out that social investments are rather akin to traditional welfare state programs, and are explained by similar institutional, political and economic factors. More importantly, they do not develop at the expense of income protection. Social investment initiatives are consistent with the usual politics of the welfare state and, overall, they are not inimical to the poor.
Does Survey Nonresponse Bias Estimates of Religious Service Attendance? Evidence from an Address-Based Sample from the Boston Area
Authors: Brenner Philip S 
Published: August 2018

Abstract
This study investigates what role, if any, nonresponse plays in inflating survey estimates of religious behavior, using a multimode survey designed to allow estimation of nonresponse bias. A sample of 3,000 Boston-area households drawn from an address-based frame was randomly divided into two subsamples, contacted by mail, and invited to participate in a survey. The first subsample was asked to complete an interactive voice response interview. The second subsample was asked to complete a survey by telephone if a number was available for the address or by personal interview if not. Finally, random samples of nonrespondents were recontacted for a personal interview. Comparison of attendance estimates from initial interviews with nonrespondent interviews within sample segments yields minor or minimal differences that are not statistically significant. Findings suggest that the mechanism generating survey nonresponse is unlikely to be a major cause of bias in religious service attendance estimates in this study.
Warning For Oral Drugs Containing Benzocaine
Authors: Aschenbrenner Diane S. 
Published: August 2018

Benzocaine, a local anesthetic found in over-the-counter and prescription oral drugs, is associated with a rare serious adverse effect called methemoglobinemia.The Food and Drug Administration has asked manufacturers to stop marketing benzocaine products for the treatment of teething pain in infants and oral pain in children under two years of age.
Urgent Repositioning After Venous Air Embolism During Intracranial Surgery in the Seated Position: A Case Series
Authors: Abcejo Arnoley S. , Pasternak Jeffrey J. , Perkins William J. 
Published: August 2018

Background:
Venous air embolism (VAE) is a well-described complication of neurosurgical procedures performed in the seated position. Although most often clinically insignificant, VAE may result in hemodynamic or neurological compromise resulting in urgent change to a level position. The incidence, intraoperative course, and outcome in such patients are provided in this large retrospective study.

Methods:
Patients undergoing a neurosurgical procedure in the seated position at a single institution between January 2000 and October 2013 were identified. Corresponding medical records, neurosurgical operative reports, and computerized anesthetic records were searched for intraoperative VAE diagnosis. Extreme VAE was defined as a case in which urgent seated to level position change was performed for patient safety. Detailed examples of extreme VAE cases are described, including their intraoperative course, VAE management, and postoperative outcomes.

Results:
There were 8 extreme VAE (0.47% incidence), 6 during suboccipital craniotomy (1.5%) and 2 during deep brain stimulator implantation (0.6%). VAE-associated end-expired CO2 and mean arterial pressure reductions rapidly normalized following position change. No new neurological deficits or cardiac events associated with extreme VAE were observed. In 5 of 8, surgery was completed. Central venous catheter placement and aspiration during VAE played no demonstrable role in patient outcome.

Conclusions:
Extreme VAE during seated intracranial neurosurgical procedures is infrequent. Extreme VAE-associated CO2 exchange and hemodynamic consequences from VAE were transient, recovering quickly back to baseline without significant neurological or cardiopulmonary morbidity.
Medical Physics: Quality and Safety in the Cloud
Authors: Leuenberger Ronald , Kocak Ryan , Jordan David W. , George Tim 
Published: August 2018

Abstract
Science and technology have outpaced our human ability to process and analyze the myriad data systems that extend throughout an enterprise of health care networks. Medical physicists must learn to work collaboratively with computer programmers, data scientists, administrators, and health care providers in the data-rich environment of modern health care, embracing and practicing a new discipline: cloud-based medical physics. This article addresses four distinct topics: (1) Evolution of health care systems, networks and electronic medical records (EMR); (2) Evolution of medical physics with scientific discoveries and technological advancements; (3) Evolution of information technology including; metadata, enterprise and the cloud; and (4) Medical physics enterprise: adaptive approach to quality and safety for the 21st Century.
Investigation of Dose Rates Exterior to an Above-Ground Waste Storage Facility Using Radiation Transport Models
Authors: Mann Jenelle Elicia , Zoeger Norbert , Koppitsch Roman , Brandl Alexander 
Published: August 2018

Abstract
The dose rate profile at different heights above the ground and as a function of distance from the north, west, and south walls of an above-ground waste storage facility was analyzed using the Monte Carlo n-Particle Transport eXtended (MCNPX) radiation transport code. The waste storage facility houses 9,996 waste barrels of conditioned waste. The facility has concrete shielding added to the building walls on the north, west, and east sides, with no such additional shielding towards the roof or the south side wall; instead, the distance from the first row of barrels to the wall is extended to allow for maneuverability of a crane on the south side. The dose rate is computed as a function of distance using MCNPX and assuming a homogeneous 60Co distribution in each waste barrel. Different dose regions are identified and analyzed based on graphical features and best-fit functions. The dose rates were expected to be largest at the wall of the facility and subsequently decrease continuously with distance from the repository; however, our analysis indicates a peak in dose rate observed for all heights on the north and west sides of the facility. This peak is likely due to scattering in the shielding material and atmosphere, and possibly could be ascribed to skyshine. The difference between the dose rate at 1 m outside the wall and the peak dose rate is significant, and indicates that the dose rate measured close to the wall may not always be conservative for extended sources, such as an above-ground waste storage facility.
DILUTE POVIDONE-IODINE PROPHYLAXIS MAINTAINS SAFETY WHILE IMPROVING PATIENT COMFORT AFTER INTRAVITREAL INJECTIONS
Authors: Peden Marc C. , Hammer Mark E. , Suñer Ivan J. 
Published: August 2018

Purpose:
To report the rates of postintravitreal injection (IVT) endophthalmitis with topical conjunctival application of various concentrations of povidone-iodine (PI), including no PI.

Methods:
Retrospective chart review of patients receiving IVTs performed in a single practice between January 2011 and June 2016. Concentration of PI for all injections was recorded and cases of endophthalmitis identified and reviewed.

Results:
A total of 35,060 IVTs in 1854 patients were included from the 5.5-year period. 29,281 injections were performed with standard 5% PI, 5,460 injections with diluted PI (3,731 with 2.5%, 1,673 with 1.25%, 56 with 0.625%), and 319 IVTs with no PI. Incidence of patient-reported PI sensitivity occurred in 15.9% of patients. Fourteen cases of endophthalmitis were identified: 12 in eyes that received 5% PI, one in an eye that received 1.25% PI, and one in an eye receiving no PI. The incidence of endophthalmitis was 0.04% for 5% PI, 0.02% for dilute PI, and 0.31% for no PI prophylaxis. All cases underwent prompt vitrectomy and had positive cultures for coagulase-negative Staphylococcus.

Conclusion:
Application of dilute PI solution to the conjunctiva at the time of IVT is an effective alternative to 5% PI for endophthalmitis prophylaxis in betadine-sensitive patients.
A Cost-Effective Myoelectric Prosthetic Hand
Authors: Atique MD Moin , Rabbani Siddique-e 
Published: August 2018

ABSTRACT

Introduction
A cost-effective myoelectric prosthetic hand for persons with wrist amputations is a need for developing countries. Instead of trying to develop manipulation of all the fingers, which would be complex, expensive, and demanding on battery power, we took an approach to make the design simple but moderately usable.

Methods and Materials
Because a sizable number of tasks can be done by controlling the thumb only, we anticipate that it would be an efficient design where the user will control only the thumb using electromyographic (EMG) signals. The shape of the hand is such that it will let the user hold small objects, such as a pen. A mannequin's hand was used as the structure, and after specific modification, the necessary circuitry was set up. Surface electrodes were used to acquire the EMG signals, which were then amplified using a bioelectric amplifier specifically designed and developed for this purpose. A microcontroller-based interface detects EMG and controls the DC gear motor that moves the thumb.

Results
The thumb of the developed unit responded to contraction of the arm muscles as desired. The user can control the thumb using his or her EMG signal and write holding a pen. A box-and-blocks test was conducted in which, on average, the user was able to move 6.6 blocks per minute.

Conclusions
The design is moderately usable but needs some minor improvements before practical use.
Evaluation of the Loads Applied on the Hip Joints in Walking with and without Scottish Rite Orthosis in Subjects with Perthes Disease: A Pilot Study
Authors: Karimi Mohammad Taghi 
Published: August 2018

ABSTRACT

Introduction
Although the main aims of treatment in Legg-Calvé-Perthes disease are to increase the containment of the femoral head within the acetabulum and to decrease the loads applied to the hip joint, none of the treatment approaches have been successful. There has been no research evaluating the effect of using an orthosis on joint reaction forces in the subjects with Perthes disease. Therefore, the aim of this study was to evaluate the joint reaction forces in the subject with this disease while walking with and without orthosis.

Methods
Two subjects with Perthes disease participated in this study. They were asked to walk with and without Scottish Rite orthosis. Open SIMM software was used to extract the joint reaction forces in both conditions. The difference between kinetic and kinematic parameters in walking with and without orthosis for each subject was evaluated by two-sample t-test.

Results
The results of this study showed that the ground reaction force applied on the leg increased. Use of orthosis influenced the kinematics of hip joint and pelvis.

Conclusion
Since joint reaction force is one of the main parameters influencing hip joint deformation, use of orthosis may not influence the final deformation. As this was a pilot study, it is recommended to do research with a larger number of subjects.