bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterotrimeric Gα12/13proteins in kidney injury and disease
Authors: Tutunea-Fatan Elena , Lee Jasper C. , Denker Bradley M. , Gunaratnam Lakshman
Published: January 2020

Gα12and Gα13are ubiquitous members of the heterotrimeric guanine nucleotide-binding protein (G protein) family that play central and integrative roles in the regulation of signal transduction cascades within various cell types in the kidney. Gα12/Gα13proteins enable the kidney to adapt to an ever-changing environment by transducing stimuli from cell surface receptors and accessory proteins to effector systems. Therefore, perturbations in Gα12/Gα13levels or their activity can contribute to the pathogenesis of various renal diseases, including renal cancer. This review will highlight and discuss the complex and expanding roles of Gα12/Gα13proteins on distinct renal pathologies, with emphasis on more recently reported findings. Deciphering how the different Gα12/Gα13interaction networks participate in the onset and development of renal diseases may lead to the discovery of new therapeutic strategies.
Beclin 1/Bcl-2 complex-dependent autophagy activity modulates renal susceptibility to ischemia-reperfusion injury and mediates renoprotection by Klotho
Authors: Li Peng , Shi Mingjun , Maique Jenny , Shaffer Joy , Yan Shirley , Moe Orson W. , Hu Ming Chang
Published: January 2020

Klotho- and beclin 1-driven autophagy extends life. We examined the role of beclin 1 in modifying acute kidney injury (AKI) and whether beclin 1 mediates Klotho’s known renoprotective action in AKI. AKI was induced by ischemia-reperfusion injury in mice with different levels of autophagy activity by genetic manipulation: wild-type (WT) mice with normal beclin 1 expression and function, mice with normal beclin 1 levels but high activity through knockin of gain-of-function mutant beclin 1 ( Becn1F121A), mice with low beclin 1 levels and activity caused by heterozygous global deletion of beclin 1 ( Becn1+/−), or mice with extremely low beclin 1 activity from knockin of the mutant constitutively active beclin 1 inhibitor Bcl-2 ( Bcl2AAA). Klotho was increased by transgenic overexpression ( Tg-Kl) or recombinant Klotho protein administration. After ischemia-reperfusion injury, Becn1F121A mice (high autophagy) had milder AKI and Becn1+/− and Bcl2AAA mice (low autophagy) had more severe AKI than WT mice. Tg-Kl mice had milder AKI, but its renoprotection was partially attenuated in Becn1+/− ;Tg-Kl mice and was significantly reduced, although not completely abolished, in Bcl2AAA;Tg-Kl mice. Recombinant Klotho protein conferred more renoprotection from AKI in WT mice than in Becn1+/− or Bcl2AAA mice. Klotho reduced beclin 1/Bcl-2 protein complexes and increased autophagy activity, but this effect was less prominent in mice or cells with Bcl2AAA. Transfected Bcl2AAA or Becn1F123A decreased or increased autophagy activity and rendered cells more susceptible or more resistant to oxidative cytotoxicity, respectively. In conclusion, beclin 1 confers renoprotection by activating autophagy. Klotho protects the kidney partially via disruption of beclin 1/Bcl-2 interactions and enhancement of autophagy activity.
Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells
Authors: Shotorbani Parisa Yazdizadeh , Chaudhari Sarika , Tao Yu , Tsiokas Leonidas , Ma Rong
Published: January 2020

Overproduction of extracellular matrix proteins, including fibronectin by mesangial cells (MCs), contributes to diabetic nephropathy. Inhibitor of myogenic differentiation family isoform a (I-mfa) is a multifunctional cytosolic protein functioning as a transcriptional modulator or plasma channel protein regulator. However, its renal effects are unknown. The present study was conducted to determine whether I-mfa regulated fibronectin production by glomerular MCs. In human MCs, overexpression of I-mfa significantly increased fibronectin abundance. Silencing I-mfa significantly reduced the level of fibronectin mRNA and blunted transforming growth factor-β1-stimulated production of fibronectin. We further found that high glucose increased I-mfa protein content in a time course (≥48 h) and concentration (≥25 mM)-dependent manner. Although high glucose exposure increased I-mfa at the protein level, it did not significantly alter transcripts of I-mfa in MCs. Furthermore, the abundance of I-mfa protein was significantly increased in the renal cortex of rats with diabetic nephropathy. The I-mfa protein level was also elevated in the glomerulus of mice with diabetic kidney disease. However, there was no significant difference in glomerular I-mfa mRNA levels between mice with and without diabetic nephropathy. Moreover, H2O2significantly increased I-mfa protein abundance in a dose-dependent manner in cultured human MCs. The antioxidants polyethylene glycol-catalase, ammonium pyrrolidithiocarbamate, and N-acetylcysteine significantly blocked the high glucose-induced increase of I-mfa protein. Taken together, our results suggest that I-mfa, increased by high glucose/diabetes through the production of reactive oxygen species, stimulates fibronectin production by MCs.
Acid-sensing ion channels in sensory signaling
Authors: Carattino Marcelo D. , Montalbetti Nicolas
Published: January 2020

Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.
Adenosine inhibits the basolateral Cl−ClC-K2/b channel in collecting duct intercalated cells
Authors: Zaika Oleg , Tomilin Viktor N. , Pochynyuk Oleh
Published: January 2020

Adenosine plays an important role in various aspects of kidney physiology, but the specific targets and mechanisms of actions are not completely understood. The collecting duct has the highest expression of adenosine receptors, particularly adenosine A1receptors (A1Rs). Interstitial adenosine levels are greatly increased up to a micromolar range in response to dietary salt loading. We have previously shown that the basolateral membrane of principal cells has primarily K+conductance mediated by Kir4.1/5.1 channels to mediate K+recycling and to set up a favorable driving force for Na+/K+exchange ( 47 ). Intercalated cells express the Cl−ClC-K2/b channel mediating transcellular Cl−reabsorption. Using patch-clamp electrophysiology in freshly isolated mouse collecting ducts, we found that acute application of adenosine reversely inhibits ClC-K2/b open probability from 0.31 ± 0.04 to 0.17 ± 0.06 and to 0.10 ± 0.05 for 1 and 10 µM, respectively. In contrast, adenosine (10 µM) had no measureable effect on Kir4.1/5.1 channel activity in principal cells. The inhibitory effect of adenosine on ClC-K2/b was abolished in the presence of the A1R blocker 8-cyclopentyl-1,3-dipropylxanthine (10 µM). Consistently, application of the A1R agonist N6-cyclohexyladenosine (1 µM) recapitulated the inhibitory action of adenosine on ClC-K2/b open probability. The effects of adenosine signaling in the collecting duct were independent from its purinergic counterpartner, ATP, having no measurable actions on ClC-K2/b and Kir4.1/5.1. Overall, we demonstrated that adenosine selectively inhibits ClC-K2/b activity in intercalated cells by targeting A1Rs. We propose that inhibition of transcellular Cl−reabsorption in the collecting duct by adenosine would aid in augmenting NaCl excretion during high salt intake.
Infrared Small Target Detection with Total Variation and Reweighted ℓ1 Regularization
Authors: Fang Houzhang , Chen Min , Liu Xiyang , Yao Shoukui
Published: January 2020

Infrared small target detection plays an important role in infrared search and tracking systems applications. It is difficult to perform target detection when only a single image with complex background clutters and noise is available, where the key is to suppress the complex background clutters and noise while enhancing the small target. In this paper, we propose a novel model for separating the background from the small target based on nonlocal self-similarity for infrared patch-image. A total variation-based regularization term for the small target image is incorporated into the model to suppress the residual background clutters and noise while enhancing the smoothness of the solution. Furthermore, a reweighted sparse constraint is imposed for the small target image to remove the nontarget points while better highlighting the small target. For higher computational efficiency, an adapted version of the alternating direction method of multipliers is employed to solve the resulting minimization problem. Comparative experiments with synthetic and real data demonstrate that the proposed method is superior in detection performance to the state-of-the-art methods in terms of both objective measure and visual quality.
A Case of Comorbid PTSD and Posttraumatic OCD Treated with Sertraline-Aripiprazole Augmentation
Authors: Rossi Rodolfo , Niolu Cinzia , Siracusano Alberto , Rossi Alessandro , Di Lorenzo Giorgio
Published: January 2020

Several studies report on traumatic history in Obsessive Compulsive Disorder (OCD) and comorbidity between Posttraumatic Stress Disorder (PTSD) and OCD. First-line pharmacological treatments for both OCD and PTSD are primarily based on antidepressants, including Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRI) such as Venlafaxine for PTSD. Second-Generation Antipsychotic (SGA) augmentation has shown good outcomes for nonresponsive OCD cases. However, evidence on the use of SGA in PTSD is more limited. In the present paper, we report on comorbid OCD-PTSD successfully treated with aripiprazole augmentation of sertraline. Shared psychopathological and pharmacological aspects of the disorders are discussed.
Assessment of Family Planning Counseling Provided for Postpartum Women and Associated Factors
Authors: Abdulreshid Munit , Dadi Hailemichael B.
Published: January 2020

Background. Good quality family planning counseling particularly in the postpartum period is paramount to contraception adoption and continuation; it is also paramount in the reduction of maternal as well as infant morbidity and mortality. Objective. Assess the level of family planning counseling provided for women in their immediate postpartum period in the labor ward at Saint Paul’s Hospital in 2019. Method. An institution-based cross-sectional study was conducted from February to March of 2019 among women in the labor ward. A face-to-face exit interview was conducted with 209 randomly selected women. A structured pretested questionnaire was used to assess the level of family planning counseling provided. Bivariate logistic regression was used to test for statistical association. Results. Only 28.2% of the counseling sessions were adequate. Most (58.9%) of the counseling sessions did not maintain the privacy of the client. In 67.9% of the sessions, the counselor did not ask the concern of the client regarding the use of modern family planning methods and 74.2% of the clients were not told about the possible side effects of a method. Clients with no formal education (OR=2.52, 95%CI=1.1‐3.3) and those with only primary level education (OR=1.22, 95%CI=1.04‐3.02) were more likely to have had inadequate counseling. Conclusion. The level of family planning counseling was inadequate. The study indicated the need to provide training for service providers on family planning counseling with the existing standard frameworks but also in consideration of the sociodemographic background of the client, particularly their educational status.
UHPLC‐ESI‐Orbitrap‐MS Analysis of Biologically Active Extracts from Gynura procumbens (Lour.) Merr. and Cleome gynandra L. Leaves
Authors: Chandradevan Machap , Simoh Sanimah , Mediani Ahmed , Ismail Nor Hadiani , Ismail Intan Safinar , Abas Faridah
Published: January 2020

This study aimed to determine the total phenolic content, DPPH scavenging, α‐glucosidase, and nitric oxide (NO) inhibition of Gynura procumbens and Cleome gynandra extracts obtained with five different ethanolic concentrations. The findings showed that the 100% ethanolic extract of G. procumbens had the highest phenolic content and the lowest IC50 values for DPPH scavenging and NO inhibition activity compared to the properties of the other extracts. For C. gynandra, the 20% and 100% ethanolic extracts had comparably high total phenolic contents, and the latter possessed the lowest IC50 value in the NO inhibition assay. In addition, the 20% ethanolic extract of C. gynandra had the lowest IC50 value in the DPPH scavenging assay. However, none of the extracts from either herb had the ability to inhibit α‐glucosidase enzyme. Pearson correlation analysis indicated a strong relationship between the phenolic content and DPPH scavenging activity in both herb extracts. A moderately strong relationship was also observed between the phenolic content and NO inhibition in G. procumbens extracts and not in C. gynandra extracts. The UHPLC‐ESI‐Orbitrap‐MS revealed major phenolics from the groups of hydroxycinnamic acids, hydroxybenzoic acids, and flavonoid derivatives from both herbs, which could be the key contributors to their bioactivities. Among the identified metabolites, 24 metabolites were tentatively assigned for the first time from both species of studied herbs. These two herbs could be recommended as prospective natural products with valuable medicinal properties.
Integrating Caregiver Support into Multiple Sclerosis Care
Authors: Martindale-Adams Jennifer , Zuber Jeffrey , Levin Michael , Burns Robert , Graney Marshall , Nichols Linda O.
Published: January 2020

With loss of mobility in Multiple Sclerosis (MS) comes increase in caregiver assistance, burden, stress, and depression. This 6-month feasibility study used a pre-post design to test integration of a validated, behavioral, caregiving intervention into an ongoing MS clinic. Because the program focused on caregivers, there were no additional services provided to the persons living with MS other than usual medical care. Twenty-five MS caregivers received REACH VA (Resources for Enhancing All Caregivers’ Health in the VA), a six-session behavior-focused intervention during two to three months designed to increase caregiver skills in managing their own stress and burden and MS related issues and concerns, with a focus on mobility. Caregivers were assessed at baseline, three, and six months. Caregivers’ expectations of the program were to receive education on MS, caregiving and stress management skills, and support. The major benefits caregivers reported were understanding their loved one’s condition and how to better provide care. At six months, caregivers reported statistically and clinically significant improvements in depressive symptoms and bother with challenging MS behaviors. Persons with MS reported benefit for their caregivers and for themselves; 71% reported that their caregivers had helped them with mobility and function. Study results suggest that the addition of the brief REACH caregiver intervention into an MS clinic would benefit both caregivers and persons with MS. Although the intervention was six sessions over three months, benefit persisted at six months, suggesting durability of effects. This trial is registered with ClinicalTrials.gov NCT02835677.
Analytical Solution for Lateral‐Torsional Buckling of Concrete‐Filled Tubular Flange Girders with Torsional Bracing
Authors: Liu Yingchun , Hang Zhaoming , Zhang Wenfu , Chen Keshan , Ji Jing
Published: January 2020

Concrete‐filled tubular flange girders have been used in bridges, and torsional bracings are widely used in them to increase the lateral‐torsional buckling strength. This article proposes an analytical solution for the lateral‐torsional buckling (LTB) of concrete‐filled tubular flange steel girders with torsional bracing under a concentrated load. The modal trial functions of lateral displacement and the torsional angle are expressed by the first six terms of the trigonometric function. By introducing dimensionless parameters, the variational solution of energy for the buckling equation of the LTB of the girders is obtained, and the formula for the dimensionless critical moment of its LTB is derived using 1stOpt based on 32,550 data sets. Compared with the finite element method, the proposed critical formula is highly accurate and can be applied to engineering design. Finally, parametric studies were conducted on the effects of the stiffness of torsional bracing, the span of the girder, and the flange steel ratio.
Improved Continuous Wavelet Transform for Modal Parameter Identification of Long-Span Bridges
Authors: Zhang Mingjin , Huang Xu , Li Yongle , Sun Hao , Zhang Jingyu , Huang Bin
Published: January 2020

Accurate and timely identification of modal parameters of long-span bridges is important for bridge health monitoring and wind tunnel tests. Wavelet analysis is one of the most advantageous methods for identification because of its good localization characteristics in both time and frequency domain. In recent years, the wavelet method has been applied more frequently in parameter identification of linear and nonlinear systems. In this article, based on wavelet ridges and wavelet skeleton, the improved modal parameter identification method was studied. To find the appropriate time-frequency resolution, an optimal wavelet basis design principle based on minimum Shannon entropy was proposed. Aiming at endpoint effect in wavelet transform, a prediction continuation method based on support vector machine (SVM) was proposed, which can effectively suppress the endpoint effect of the extended samples. In view of the fact that the ridges of metric matrices obtained by the traditional crazy climber algorithm cannot fully reflect the distribution of ridges of modulus value matrices of wavelet coefficients, an improved high-precision crazy climber algorithm was put forward to accurately identify the position of the ridge of wavelet coefficients. Finally, taking a long-span cable-stayed bridge and a long-span suspension bridge as the engineering background, improved continuous wavelet transform (CWT) was applied to modal parameter identification of bridge under ambient excitation. The modal parameters such as modal frequency, damping ratio, and mode shape were obtained. Compared with the calculation value of the numerical simulation of long-span cable-stayed bridge and wind tunnel test of long-span suspension bridge, the reliability of CWT for modal parameter identification of long-span bridges under ambient excitation was verified.
The Role of Establishing a Multidisciplinary Team for Idiopathic Granulomatous Mastitis in Improving Patient Outcomes and Spreading Awareness about Recent Disease Trends
Authors: Yaghan Rami J. , Ayoub Nehad M. , Hamouri Shadi , Al-Mohtaseb Alia , Gharaibeh Maha , Yaghan Lamees , Al-Dari Mahmoud , Al-Kaff Hiba , Al-Zoubi Nabil A.
Published: January 2020

Background. Iidiopathic granulomatous mastitis (IGM) is stereotypically described as a mysterious entity that mimics breast carcinoma imposing management challenges. In 2002, we established a multidisciplinary team to treat patients with IGM. This study aimed to evaluate the role of this team in improving patient outcomes. Also, a review of literature is provided to highlight recent disease trends. Patients and Methods. Pertinent data for 44 patients treated for IGM from 2002 to 2018 were analyzed and compared to data prior to 2002. Results. Mean age at diagnosis was 37.9 years ± 6.4. The diagnosis of IGM was confirmed by True-cut biopsy (TCB), Frozen section (FS), and surgical biopsy in 70.5%, 25%, and 4.5% of patients, respectively. FS was used to assess the resection margins in three patients. Suspicion for malignancy was raised in one out of 39 ultrasound reports, and one out of 20 mammography reports. Wide local excision was the main treatment modality (95.5%). 19 patients (43.2%) received corticosteroids. Prior to 2002, IGM was only recognized after surgical resection with a 71% initial false impression of carcinoma. After 2002, the initial false clinical impression of carcinoma dropped to 29.5%. Recurrence rate was 31.82%. Younger age at diagnosis was significantly associated with recurrence (χ2 = 5.598; p=0.018). Chi-square analysis showed no significant association between BMI and recurrence (χ2 = 0.776; p=0.678). Conclusion. The establishment of a multidisciplinary team for IGM was associated with a reduced erroneous impression of breast cancer, and a reduced false positive radiological diagnosis of breast carcinoma. FS was a useful confirmatory procedure. Our series included the first case of a diffuse papular rash as a systemic manifestation of IGM. Recent literature indicates that IGM is changing its face. IGM is being reported in all age groups, and even in males. The clinical manifestations have markedly expanded. Diagnosis by TCB has replaced blind surgical excision. More data regarding predictors of recurrence is accumulating.
Objectively Measured Physical Activity and Its Association with Functional Independence, Quality of Life and In-Hospital Course of Recovery in Elderly Patients with Proximal Femur Fractures: A Prospective Cohort Study
Authors: Marsault Laureen V. , Ryg Jesper , Madsen Carsten Fladmose , Holsgaard-Larsen Anders , Lauritsen Jens , Schmal Hagen
Published: January 2020

Background. Physical activity in elderly patients is crucial for recovery from proximal femoral fractures. Considering the limited possibilities for objective measurement, we aimed to evaluate the use of an accelerometer in this population to determine activity’s association with functional independence, quality of life, and course of recovery. Methods. 52 patients undergoing operative treatment for proximal femur fractures (81.3 ± 7.5 years) were included in a prospective cohort study. 12 patients with fall but without fracture of the lower extremities (80.8 ± 9.5 years) served as control. An Axivity AX3 tracker continuously recorded signal vector magnitudes during the hospital stay. Additionally, 2 ± 1 and 8 ± 3 days (time point 1 and 2) after operation EuroQol-5D and Barthel-20 indices were evaluated. Results. Physical activity increased in all patients with time. Multiple regression analyses revealed that a high Barthel-20 before fracture, a low age, a high body mass index, high albumin, and low C-reactive protein levels were independent predictors for high physical activity at time point 1 (p<0.05). Physical activity correlated significantly with EuroQol-5D and Barthel-20 at time point 1 and 2 (p<0.02). Furthermore, physical activity at time point 1 predicted EuroQol-5D, physical activity, and Barthel-20 at time point 2 (p<0.01). A multiple regression demonstrated equal physical activity in patients with or without a hip fracture. Conclusions. Accelerometer signals correlate with postoperative physical activity, Barthel-20 and quality of life in elderly patients. Physical activity is thereby positively influenced by a high prefall functional independence and a good nutrition status. A timely and adequate operation provided, there is no difference between patients with or without a fracture. This trial is registered with DRKS 00011934 on 10th April 2017.
Effect of Welding Residual Stress on Along-Wind Fatigue Life of Welded Joints in Guyed Mast
Authors: Qu Weilian , Wang Min , Zhou Qiang
Published: January 2020

On the premise of only considering along-wind effect on guyed mast, the influence of welding residual stress on the fatigue life of welded joints is evaluated in this paper. Since the sum of residual stress and along-wind-induced dynamic stress exceeds the yield strength of structural steel, the effect of residual stress relaxation is included in the numerical analysis. The multiscale finite element analysis of guyed mast is developed in order to capture accurately stress field distribution of welded joint for the “welding-wind-induced” case in which both residual stress and along-wind-induced stress are taken into consideration, and the stress response characteristics at fatigue critical point of welded joints are pointed out. It is found that the “welding-wind-induced” stress field of welded joint can be approximately considered as multiaxial proportional loading state and hence the stress-based von Mises criterion can be adopted to evaluate the fatigue life of welded joints. Based on the S-N curve of stress fatigue life for welded specimens with structural steel commonly used in guyed masts, the fatigue damage of key welded joints is predicted, and as a consequence, the influence of welding residual stress on the fatigue life of welded joints is discussed.
Prevalence and Associated Factors of Tuberculosis among Adult Household Contacts of Smear Positive Pulmonary Tuberculosis Patients Treated in Public Health Facilities of Haramaya District, Oromia Region, Eastern Ethiopia
Authors: Adane Abinet , Damena Melake , Weldegebreal Fitsum , Mohammed Hussein
Published: January 2020

Background. Tuberculosis is an infectious airborne disease caused by Mycobacterium tuberculosis. It still remains a major public health problem which affects all age groups. Risk of exposure is higher in household contact than members of the general population. Objective. The aim of this study was to assess the prevalence and associated factors of tuberculosis among adult household contacts of smear positive pulmonary tuberculosis in Haramaya district, Oromia Region, Eastern Ethiopia from February to March, 2019. Method. A community based cross-sectional study design was conducted. A total of 454 study participants were selected using systematic sampling method from all adult household contacts of smear positive pulmonary tuberculosis patients treated from July 2017 to December 2018. Data were collected using a pretested and structured questionnaire; and laboratory examination was processed using fluorescent smear microscope. Logistic regression analysis was used to identify the factors associated with the infection of pulmonary tuberculosis and a statistically significant association was declared at P-value < 0.05. Result. The overall prevalence of pulmonary tuberculosis among adult household contacts was 7.8% (95% CI: 5.8–10.0). The risk factors for tuberculosis infection among household contacts were eating meals less than three times per day (AOR = 4.31; 95% CI: 1.61, 11.55), drinking raw milk (AOR = 4.12; 95% CI: 1.43, 11.90), having family history of tuberculosis with more than one index case (AOR = 2.7; 95% CI: 1.02, 6.92), living in poor ventilated houses (AOR = 4.02; 95% CI: 1.38, 11.76), and living in inadequate size of living room (AOR = 3.4; 95% CI: 1.30, 8.86). Conclusion. In this study, the prevalence of tuberculosis among adult household contacts of smear positive pulmonary tuberculosis is high. Eating meals less than three times per day, drinking raw milk, living in poor ventilated houses, and inadequate sizes of the rooms were identified as contributing factors. Therefore, we recommend that the transmission of tuberculosis can potentially be reduced by a better contact tracing and treatment strategies along with appropriate health education.
An Adaptive Data-Driven Approach to Solve Real-World Vehicle Routing Problems in Logistics
Authors: Žunić Emir , Đonko Dženana , Buza Emir
Published: January 2020

Transportation occupies one-third of the amount in the logistics costs, and accordingly transportation systems largely influence the performance of the logistics system. This work presents an adaptive data-driven innovative modular approach for solving the real-world vehicle routing problems (VRPs) in the field of logistics. The work consists of two basic units: (i) an innovative multistep algorithm for successful and entirely feasible solving of the VRPs in logistics and (ii) an adaptive approach for adjusting and setting up parameters and constants of the proposed algorithm. The proposed algorithm combines several data transformation approaches, heuristics, and Tabu search. Moreover, as the performance of the algorithm depends on the set of control parameters and constants, a predictive model that adaptively adjusts these parameters and constants according to historical data is proposed. A comparison of the acquired results has been made using the decision support system with predictive models: generalized linear models (GLMs) and support vector machine (SVM). The algorithm, along with the control parameters, which uses the prediction method, was acquired and was incorporated into a web-based enterprise system, which is in use in several big distribution companies in Bosnia and Herzegovina. The results of the proposed algorithm were compared with a set of benchmark instances and validated over real benchmark instances as well. The successful feasibility of the given routes, in a real environment, is also presented.
An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants
Authors: Mujer Mark Terence P. , Rai Manoj P. , Atti Varunsiri , Dimaandal Ian Limuel , Chan Abigail S. , Shrotriya Shiva , Gundabolu Krishna , Dhakal Prajwal
Published: January 2020

Non-vitamin K antagonist oral anticoagulants (NOACs) include thrombin inhibitor dabigatran and coagulation factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs have several benefits over warfarin, including faster time to the achieve effect, rapid onset of action, fewer documented food and drug interactions, lack of need for routine INR monitoring, and improved patient satisfaction. Local hemostatic measures, supportive care, and withholding the next NOAC dose are usually sufficient to achieve hemostasis among patients presenting with minor bleeding. The administration of reversal agents should be considered in patients on NOAC's with major bleeding manifestations (life-threatening bleeding, or major uncontrolled bleeding), or those who require rapid anticoagulant reversal for an emergent surgical procedure. The Food and Drug Administration (FDA) has approved two reversal agents for NOACs: idarucizumab for dabigatran and andexanet alfa for apixaban and rivaroxaban. The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) have released an updated guideline for the management of patients with atrial fibrillation that provides indications for the use of these reversal agents. In addition, the final results of the ANNEXA-4 study that evaluated the efficacy and safety of andexanet alfa were recently published. Several agents are in different phases of clinical trials, and among them, ciraparantag has shown promising results. However, their higher cost and limited availability remains a concern. Here, we provide a brief review of the available reversal agents for NOACs (nonspecific and specific), recent updates on reversal strategies, lab parameters (including point-of-care tests), NOAC resumption, and agents in development.
Effects of BRCA Germline Mutations on Triple-Negative Breast Cancer Prognosis
Authors: Pogoda Katarzyna , Niwińska Anna , Sarnowska Elżbieta , Nowakowska Dorota , Jagiełło-Gruszfeld Agnieszka , Siedlecki Janusz , Nowecki Zbigniew
Published: January 2020

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.
An IDM‐Based Approach for Information Requirement in Prefabricated Construction
Authors: Xu Zhao , Abualdenien Jimmy , Liu Hao , Kang Rui
Published: January 2020

Prefabricated construction promotes providing better productivity and project results. Building models, including their elements’ fabrication details, are complex structures that need accurate information delivery among the project participants and their partial designs. This paper extends the IFC data model to support prefabricated construction. Also, it discusses the advantages of systematically managing exchange requirements in a database to facilitate generating IDM (Information Delivery Manual). The paper first introduces a BIM‐based collaborative work mode by sharing and extracting the model views. The core of the sharing is the establishment of view exchange standard about the linked model and the definition of exchange requirements based on the design process, leading to the formulation of the IDM standard again from the perspective of the actual design. Process maps covering architecture, structure, plumbing, mechanical engineering, and electrical engineering are made to show how to realize BIM‐based collaborative work. Then the exchange requirements referred to the object and attribute of the BIM model which should be delivered in a special phase are defined in particular tables. To facilitate the automation of managing and exchanging requirements, a database management system is designed with its corresponding user‐interface, which enhances the collaboration and delivery throughout the project life cycle. The proposed approach supports better information reuse and delivery among the project participants.
PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma
Authors: Chen Qin , Yu Wen-Ying , Zhang Huan-Huan , Zhang Song-Zhao , Fang Jie , Wu Fang , Ying Hua-Zhong , Yu Chen-Huan
Published: January 2020

PBX3 (Pre‐B‐cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3‐shRNA‐induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.
An Analysis of Biopsies for Suspected Skin Cancer at a Tertiary Care Dermatology Clinic in the Western Cape Province of South Africa
Authors: de Wet Johann , Steyn Minette , Jordaan Henry F. , Smith Rhodine , Claasens Saskya , Visser Willem I.
Published: January 2020

Background. Skin cancer is a growing health concern worldwide. It is the most common malignancy in South Africa and places a large burden on the public healthcare sector. There is a paucity of published scientific data on skin cancer in South Africa. Objectives. To report the findings of biopsies performed in patients with suspected skin cancer attending the Tygerberg Academic Hospital (TAH) Dermatology outpatient department (OPD) in the Western Cape Province of South Africa. Methodology: A retrospective chart review identified all patients who underwent a biopsy for a suspected skin cancer diagnosis between September 2015 and August 2016 at the TAH dermatology OPD. Results. A total number of 696 biopsies from 390 participants were identified, of which 460 were histologically confirmed as malignant lesions. The proportion of clinically suspected skin cancers that were histologically confirmed as cancer was 68%. The most commonly occurring malignancies were basal cell carcinoma (BCC) (54.8%), squamous cell carcinoma (SCC) (18.9%), squamous cell carcinoma in-situ (SCCI) (8.0%), Kaposi’s sarcoma (KS) (6.7%), malignant melanoma (MM) (6.1%), and keratoacanthoma (KA) (4.6%). The number needed to treat (NTT) for all cancers diagnosed and for MM was 1.5 and 4 respectively. BCC (89.3%) and KS (67.7%) was the most common skin cancer in the white and black population respectively. The ratio of BCC to SCC was 2.03. Conclusion. This study provides valuable scientific data on the accuracy of skin cancer diagnosis, distribution and patient demographics in the Western Cape Province of South Africa, on which further research can be based. The study highlights the burden of skin cancer on this specific population group and calls for standardised reporting methods and increased surveillance of skin cancers.
Reappraisal Value of a Modified Rotational Atherectomy Technique in Contemporary Coronary Angioplasty Era
Authors: Dong Haojian , Hachinohe Daisuke , Nie Zhiqiang , Kashima Yoshifumi , Luo Jianfang , Haraguchi Takuya , Shitan Hidemasa , Watanabe Tomohiko , Tadano Yutaka , Kaneko Umihiko , Sugie Takuro , Kobayashi Ken , Kanno Daitaro , Enomoto Morio , Sato Katsuhiko , Fujita Tsutomu
Published: January 2020

Objectives. To introduce a modified rotational atherectomy (RA) procedure and investigate the early and midterm outcomes of the RA-facilitating diversified percutaneous coronary intervention (PCI) in a large group of aged patients with higher cardiovascular risk. Background. Previous studies about the outcomes of RA were limited with small sample size and low-risk population. Methods. Between January 2013 and November 2015, 1169 consecutive patients treated with modified RA-facilitated PCI were retrospectively enrolled, including de novo calcified lesions and in-stent restenosis. Patients were regularly followed up for at least 1 year. Major adverse cardiac events (MACE) were analyzed for all participants by different strategies. Cox regression analysis was performed to identify risk factors for the events. Results. The median age of patients was 75 years, with 11.7% of patients on maintenance hemodialysis. Most lesions (99.9%) were complex (American Heart Association type B2/C), and 68.3% were treated with RA + drug-eluting-stent (DES). Successful angiography was achieved in 97.8% cases, with 1.7% (20/1169) experiencing coronary perforation (including guidewire perforation). The incidence of MACE was 20.5% and 26.8% at 1-year and 2-year follow-up and were mainly driven by target lesion revascularization (TLR) (10.3% and 12.5%, respectively). The strategy of RA + DES had the lowest 2-year MACE, compared with the RA + drug-coated balloon and RA + plain old balloon angioplasty (14.5%, 30.5%, and 26.0%, respectively). Conclusions. The modified RA technique is a safe and effective tool in the contemporary PCI era, even in high-risk patients. The TLR rate was relatively high but acceptable in such complex lesions.
Research on CEEMD-AGA Denoising Method and Its Application in Feed Mixer
Authors: Yang Dong , Sun Yu , Wu Kai
Published: January 2020

Rotating shaft is the key part of rotating machinery, which directly affects the performance of the whole machine. Field test is an easy and quick way to obtain the load data in engineering practice. However, because of various reasons, the load data are often mixed with many noise components. Based on the autocorrelation function, the CEEMD (complementary ensemble empirical mode decomposition) denoising method is proposed in this paper. The AGA (adaptive genetic algorithm) is adopted to solve parameter optimization problems in CEEMD. A new similarity function is proposed as the fitness function. Lastly, the proposed denoising method is applied to a feed mixer’s load which is obtained by field test. The result shows that the CEEMD-AGA method has good robustness, noise components of small stress amplitude and large stress mean are removed, and there is a high correlation between the original data and the reconstructed data, which demonstrate that the CEEMD-AGA method can reduce the influence of noise components effectively.
Facilitating Cancer Epidemiologic Efforts in Cleveland via Creation of Longitudinal De-Duplicated Patient Data Sets
Authors: Tian Ye D. , Menegay Harry , Waite Kristin A. , Saroufim Paola G. , Beno Mark F. , Barnholtz-Sloan Jill S.
Published: January 2020

Background:

Cleveland, Ohio, is home to three major hospital systems serving approximately 80% of the Northeast Ohio population. The Cleveland Clinic, University Hospitals Health System, and MetroHealth are direct competitors for primary and specialty care, and patient overlap between these systems is high. Fragmentation of health data that exist in silos at these health systems produces an overestimation of disease burden due to double and sometimes triple counting of patients. As a result, longitudinal population-based studies across the Cleveland patient population are impeded unless accurate and actionable clinically derived health data sets can be created.

Methods:

The Cleveland Institute for Computational Biology has developed the De-Duplicate and De-Identify Research Engine (DeDeRE) that, without any exchange of personal health identifiers (PHI) between health systems, will effectively de-duplicate the patients between one or more health entities.

Results:

The immediate utility of this software for cancer epidemiology is the increased accuracy in measuring cancer burden and the potential to perform longitudinal studies with de-duplicated, de-identified data sets.

Conclusions:

The DeDeRE software developed and tested here accomplishes its goals without exposing PHIs using a state-of-the-art, trusted privacy preservation network enabled by a hash-based matching algorithm.

Impact:

This paper will guide the reader through the functions currently developed in DeDeRE and how a healthcare organization (HCO) employing the release version of this technology can begin sharing data with one or more additional HCOs in a collaborative and noncompetitive manner to create a regional population health resource for cancer researchers.

See all articles in this CEBP Focus section, “Modernizing Population Science.”
Association of Anti-TNF with Decreased Survival in Steroid Refractory Ipilimumab and Anti-PD1–Treated Patients in the Dutch Melanoma Treatment Registry
Authors: Verheijden Rik J. , May Anne M. , Blank Christian U. , Aarts Maureen J.B. , van den Berkmortel Franchette W.P.J. , van den Eertwegh Alfonsus J.M. , de Groot Jan Willem B. , Boers-Sonderen Marye J. , van der Hoeven Jacobus J.M. , Hospers Geke A. , Piersma Djura , van Rijn Rozemarijn S. , ten Tije Albert J. , van der Veldt Astrid A.M. , Vreugdenhil Gerard , van Zeijl Michiel C.T. , Wouters Michel W.J.M. , Haanen John B.A.G. , Kapiteijn Ellen , Suijkerbuijk Karijn P.M.
Published: January 2020

Purpose:

Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.

Experimental Design:

Using data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.

Results:

A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade ≥3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63–0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF ± steroids for steroid-refractory toxicity compared with patients who were managed with steroids only (HRadj = 1.61; 95% CI, 1.03–2.51), with a median OS of 17 and 27 months, respectively.

Conclusions:

Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.

See related commentary by Weber and Postow, p. 2085