bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model
Authors: Alanazi Ahmed Z. , Alqahtani Faleh , Mothana Ramzi A. A. , Mohany Mohamed , Abuohashish Hatem M. , Ahmed Mohammed M. , Al-Rejaie Salim S.
Published: December 2020

Earlier studies revealed the potential therapeutic values of Loranthus regularis (L. regularis). This study evaluated Loranthus regularis (L. regularis) extract systemic antidiabetic effects and benefits against diabetic hepatocellular injuries through antioxidant and anti‐inflammatory pathways using the streptozotocin (STZ) model in Wistar albino rats. After diabetes induction, animals were orally treated with L. regularis extract for 4 weeks. Serum levels of glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglycerides (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) were estimated. Furthermore, tumor necrosis factor alpha (TNF‐α), interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), caspase‐3, nitric oxide (NO), and prostaglandin E‐2 (PGE‐2) were estimated in serum. In liver, thiobarbituric acid reactive substances (TBARSs) and reduced glutathione (GSH) as well as the proinflammatory cytokines and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reeducates (GR), and glutathione‐S‐transferase (GST) were assayed. Finally, the degree of hepatic tissue damage was evaluated histologically. Treatment of the diabetic rats with L. regularis extract markedly reduced the elevated serum levels of glucose, ALT, AST, TC, TG, LDL, TNF‐α, IL‐1β, IL‐6, caspase‐3, NO, and PGE‐2. L. regularis extract also improved serum levels of insulin and HDL. The elevated TBARS, TNF‐α, IL‐1β, and IL‐6 levels in hepatic tissue of diabetic animals were reduced by L. regularis. Moreover, L. regularis extract significantly restored the diminished hepatic GSH level and enzymatic activities of SOD, CAT, GPx, GR, and GST in diabetic animals. The biochemical protective effects of L. regularis were associated with improved histological hepatocellular integrity and architecture. Taken together, L. regularis has therapeutic effects against diabetic‐induced hepatic complications. The restored liver functions and cellular damage might be mediated through free radicals scavenging and proinflammatory cytokine inhibition.
Salivary Gland Dysfunction in Stroke Patients Is Associated with Increased Protein Glycoxidation and Nitrosative Stress
Authors: Maciejczyk Mateusz , Gerreth Piotr , Zalewska Anna , Hojan Katarzyna , Gerreth Karolina
Published: December 2020

Stroke is one of the leading causes of disability and death worldwide. Despite intensive medical care, many of the complaints directly threatening the patient’s life marginalize their dental needs after the stroke. Recent studies indicate reduced saliva secretion in stroke patients in addition to the increased incidence of caries and periodontal disease. Since oxidative stress plays a vital role in the pathogenesis of salivary gland hypofunction and neurodegenerative disorders (including stroke), this is the first to evaluate the relationship between salivary gland activity and protein glycoxidation and nitrosative damage. The content of glycation and protein oxidation products and nitrosative stress was assessed in nonstimulated (NWS) and stimulated (SWS) whole saliva of stroke patients with normal salivary secretion and hyposalivation (reduced saliva production). The study included 30 patients in the stroke’s subacute phase and 30 healthy controls matched by age and sex. We have shown that stroke patients with hyposalivation show increased contents of protein glycation (↑Amadori products and ↑advanced glycation end products), glycoxidation (↑dityrosine), and nitration (↑nitrotyrosine) products compared to stroke cases with normal salivary secretion and control group. Interestingly, higher oxidative/nitrosative stress was found in NWS, which strongly correlates with salivary flow rate, total protein content, and salivary amylase activity. Such relationships were not observed in the control group. Summarizing, oxidative and nitrosative stress may be one of the mechanisms responsible for the impairment of saliva secretion in stroke patients. However, extraglandular sources of salivary oxidative stress in stroke patients cannot be excluded. Further studies to assess salivary gland hypofunction in stroke cases are necessary.
Rapid and Nondestructive On-Site Classification Method for Consumer-Grade Plastics Based on Portable NIR Spectrometer and Machine Learning
Authors: Yang Yinglin , Zhang Xin , Yin Jianwei , Yu Xiangyang
Published: December 2020

The classification of plastic waste before recycling is of great significance to achieve effective recycling. In order to achieve rapid, nondestructive, and on-site detection, a portable near-infrared spectrometer was used in this study to obtain the diffuse reflectance spectrum for both standard and commercial plastics made by ABS, PC, PE, PET, PP, PS, and PVC. After applying a series of pretreatments, the principal component analysis (PCA) was used to analyze the cluster trend. K-nearest neighbor (KNN), support vector machine (SVM), and back propagation neural network (BPNN) classification models were developed and evaluated, respectively. The result showed that different plastics could be well separated in top three principal components space after pretreatment, and the classification models performed excellent classification results and high generalization capability. This study indicated that the portable NIR spectrometer, integrated with chemometrics, could achieve excellent performance and has great potential in the field of commercial plastic identification.
Calculation of Seven Photovoltaic Cells Parameters Using Parallelized Successive Discretization Algorithm
Authors: Deaconu Adrian M. , Cotfas Daniel T. , Cotfas Petru A.
Published: December 2020

Some parameters must be calculated with very good accuracy for the purpose of designing, simulating, and evaluating the performance of a photovoltaic system. The seven parameters of the photovoltaic cell and panels for the two-diode model are determined using a parallelized metaheuristic algorithm based on successive discretization. The parameters obtained for a photovoltaic cell and four panels using the proposed algorithm are compared with the ones calculated through over twenty methods from recent research literature. The root mean square error is used to prove the superiority of the Parallelized Successive Discretization Algorithm (PSDA). The smallest values for root mean square error (RMSE) in both cases, photovoltaic cell and panels, are obtained for the algorithm presented in this paper. The seven parameters for three panels known in the specialised literature, Kyocera KC200GT, Leibold Solar Module LSM 20, and Leybold Solar Module STE 4/100 are determined for the first time using PSDA.
The Clinical Significance of Colon Polyp Pathology in Nonalcoholic Fatty Liver Disease (NAFLD) and Its Impact on Screening Colonoscopy in Daily Practice
Authors: Lesmana Cosmas Rinaldi A. , Pakasi Levina S. , Sudoyo Aru W. , Krisnuhoni Ening , Lesmana Laurentius A.
Published: December 2020

Aim. Nonalcoholic fatty liver disease (NAFLD) has been known as a risk for the presence of colon polyp and CRC development. This study was aimed to find out the clinical significance of colon polyps’ pathology among NAFLD patients. Method. A retrospective database study was done in patients who underwent elective colonoscopy within one-year period in a referral private hospital, Jakarta. Subjects were adult patients who also had documented abdominal ultrasound (US). The association between NAFLD and colonic polyp was analyzed using Chi-square test with odds ratio (OR) and its corresponding 95% confidence interval (CI). Results. A total of 138 adult patients were enrolled; 68 (51.1%) were men. Patients’ mean age was 56.8 ± 15.3 years old. Colon polyps were found in 49 (35.5%) cases; the most common histopathology was adenoma (42.9%). NAFLD was found in 68 (49.3%) of patients. Colon polyps were found to be more among patients with NAFLD than in those without NAFLD (44.1% vs. 27.1%; OR: 2.119; 95% CI: 1.040–4.318). Colon polyps were found in 30 (44.1%) NAFLD patients, where 18 (26.5%) patients had adenomatous polyp, and from this subset of patients with adenomatous polyp, 6 (8.8%) patients had mild dysplasia, 8 (11.8%) had moderate dysplasia, 1 (1.5%) had severe dysplasia, and 3 (4.4%) had adenocarcinoma. Conclusions. NAFLD is associated with increased risk of any colon polyp, regardless of the histopathological type, compared with patients without NAFLD. This finding implies the necessity to perform screening colonoscopy in patients with NAFLD in the future.
Apicoectomy of Perforated Root Canal Using Bioceramic Cement and Photodynamic Therapy
Authors: Abu Hasna Amjad , Pereira Santos Daiane , Gavlik de Oliveira Tania Regina , Pinto Alana Barbosa Alves , Pucci César Rogerio , Lage-Marques José Luiz
Published: December 2020

Root perforation is a common endodontic accident. Its management depends mainly on root canal disinfection and sealing the perforation area by preventing any communication with the periodontium to prevent recontamination. A patient was referred to treat root perforation due to a previous treatment of tooth #22. The diagnosis was symptomatic periapical periodontitis, and the treatment plan was to retreat the root canal of #22 and make a surgical intervention (apicoectomy) associated with antimicrobial photodynamic therapy as a complementary technique. Five mineral oxides (5MO) cement was used as a root-end filling material. The procedures were performed in two sessions and controlled in two visits (after 30 days and 12 months). A bone neoformation was observed at the periapical area of tooth #22. 5MO bioceramic cement was effective in inducing the repair of the periapical lesion and had the ability to seal the exposed periapical area of the tooth. Its success depended mainly on root canal and surgical site disinfection.
Iterative Methods of Weak and Strong Convergence Theorems for the Split Common Solution of the Feasibility Problems, Generalized Equilibrium Problems, and Fixed Point Problems
Authors: Rezapour Shahram , Wang Yuanheng , Zakeri Seyyed Hasan
Published: December 2020

The purpose of this paper is to introduce the extragradient methods for solving split feasibility problems, generalized equilibrium problems, and fixed point problems involved in nonexpansive mappings and pseudocontractive mappings. We establish the results of weak and strong convergence under appropriate conditions. As applications of our three main theorems, when the mappings and their domains take different types of cases, we can obtain nine iterative approximation theorems and corollas on fixed points, variational inequality solutions, and equilibrium points.
A Mechanics Study on the Self-Righting of Abalone from the Substrate
Authors: Zhang Yun , Li Shanpeng , Zuo Pingcheng , Li Jing , Liu Jianlin
Published: December 2020

In this study, we aim to probe the self-righting behavior of abalone on a substrate based on experiments and mechanistic analyses. A successful self-righting process of abalone is observed, and its critical condition in theory can be given in terms of the rotation angle. Then, according to the moment balance and potential energy minimization, the required tension force of the abalone foot for self-righting is derived with respect to the rotation angle. The experimental result also shows that in many cases the abalone cannot finish this self-righting process. Then, measurements on the tolerant strength of abalone muscle and tolerant adhesion strength of the foot on substrate are both conducted. It is judged that the abalone muscle is strong enough, which can provide enough tension force, and thus, the self-righting mainly depends on the adhesion area of the foot on substrate. These findings cast new light on engineering new types of biomaterials and devices, such as marine equipment and soft robotics.
No Detection of SARS-CoV-2 RNA on Urethral Swab in Patients with Positive Nasopharyngeal Swab
Authors: Spirito Lorenzo , Pinchera Biagio , Patrì Angela , Delfino Mario , Imbimbo Ciro , Salvatore Paola , Gentile Ivan , Fabbrocini Gabriella
Published: December 2020

Background. The SARS-CoV-2 infection has caused one of the worst pandemics that history has ever known. SARS-CoV-2 can lead to multiple organ failure, which is life-threatening. Viral RNA is found in the lung, intestine, testicle, kidney, etc., which suggests the virus can be transmitted also via routes besides respiratory droplets. The aim of our study was to evaluate the presence of SARS-CoV-2 in urethral swabs. Methods. We enrolled ten patients with SARS-CoV-2 infection who attended the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from March 2020 to April 2020. One urethral swab and one rhino-oropharyngeal swab were collected from each patient during SARS-CoV-2 infection. Results. All ten patients had a negative urethral swab for SARS-CoV-2 RNA, whereas the rhino-oropharyngeal swab was positive for SARS-CoV-2 RNA. This finding demonstrates that, in our patients, the virus did not affect the urinary tract and therefore would not be found in the urine, and even more importantly, it would not be transmitted via urine. This result was independent of the stage of the disease. Conclusion. If confirmed in larger studies, this observation could be the key to understanding the role of SARS-CoV-2 in relation to the genitourinary system.
Cyclic Injection to Enhance Hydraulic Fracturing Efficiency: Insights from Laboratory Experiments
Authors: Kang Hao , Zhang Jincai , Fan Xin , Huang Zhiwen
Published: December 2020

In hydraulic fracturing applications, there is substantial interest to reduce the formation breakdown pressure. Previous research results show that the cyclic injection method can be used to reduce that pressure. In this study, we conducted laboratory hydraulic fracturing experiments to apply cyclic injection to reduce the breakdown pressures of very tight and strong sandstones. Experimental results show that using cyclic injection the average breakdown pressure was reduced by 18.9% in very tight sandstones and by 7.18% in normal sandstones. This indicates that the effect of cyclic injection is more significant for stronger and tighter rocks. The experiments also reveal that the rock tensile strength plays a more important role in the formation breakdown pressure with a rock strength factor of 2.85. This suggests that the breakdown pressure is higher than expected. In addition, we empirically related the breakdown pressure reduction and the injection pressure amplitude to the number of injection cycles. The curve fitting results imply that the effect of cyclic injection is more important if the number of cycles or the injection pressure amplitude is increased. Based on the results of this research, the in-situ formation breakdown pressure can be reduced by applying the cyclic injection method, and the breakdown pressure reduction is more significant as the number of cycles increases.
H

2

Control of Markovian Jump Systems with Input Saturation and Incomplete Knowledge of Transition Probabilities
Authors: Park Bum Yong
Published: December 2020

This paper proposes an

ℋ

2

state-feedback controller for Markovian jump systems with input saturation and incomplete knowledge of transition probabilities. The proposed controller is developed using second-order matrix polynomials of an incomplete transition rate to derive less conservative stabilization conditions. The proposed controller not only guarantees

ℋ

2

performance but also rejects matched disturbances. The effectiveness of the proposed method is demonstrated using three numerical examples.
Establishment of Music Emotion Model Based on Blockchain Network Environment
Authors: Xu Ke
Published: December 2020

With the innovation and development of network technology, people’s various needs are gradually increasing. Among various multimedia, music has different characteristics from other forms of multimedia. Music can contain many human emotions, and humans can express some shallow and deep emotions through music. Therefore, the study of music emotion in the context of the Internet is an area where the public is relatively concerned. In the context of new media on the Internet, based on the current music emotion model, this paper establishes a different music emotion model from the past through clear research and analysis. From music characteristics, some relative vector quantities are extracted to build samples, and the samples are screened on the basis of network media technology to build a musical emotion model. The experimental simulation results show that the music emotion model based on the blockchain network environment established in this paper has high applicability and efficiency.
Visceral Adiposity Index in Breast Cancer Survivors: A Case-Control Study
Authors: Cardoso-Peña Elías , Soto Pina Alexandra E. , Villanueva Ángel Gómez , López Chavez Gerardo Emilio , Ramírez Martínez Pablo , Ramírez Montoya Humberto , Berumen Lechuga María Guadalupe , Benitez Arciniega Alejandra Donají , Alarcón Fortepiani María de Lourdes , Valdés Ramos Roxana , Garduño García José de Jesús
Published: December 2020

Background. Breast cancer (BC) is the first cause of cancer morbidity and mortality in women. This disease has been linked to obesity; however, it is not clear how fat accumulation affects women who survive breast cancer. Although the visceral adiposity index (VAI) is a marker of cardiometabolic risk and adipose tissue dysfunction, it is not clear how it changes in breast cancer survivors. The aim of this investigation was to compare VAI in women with and without breast cancer. Methods. A case-control cross-sectional study was conducted on women who were BC survivors and women without the history of BC (control group). Body composition was assessed using electrical bioimpedance while VAI by means of waist circumference (WC), body mass index (BMI), triacylglycerols (TG), and high-density lipoprotein cholesterol (HDL-C). Results. 49 women in the BC survivor group and 50 in the control group. WC was wider in the survivor group as regards control (93.65 ± 10.48 vs. 88.52 ± 9.61 cm) (

p
=
0.025

); at once, TG and VAI were significantly higher for the survivor group (243.55 ± 199.84 vs. 159.84 ± 75.77) (

p
=
0.007

) and (11.03 ± 11.15 vs. 6.41 ± 3.66) (

p
<
0.005

), respectively. Body composition parameters were similar in both groups. Conclusions. VAI is higher in women who are BC survivors in comparison with controls matched by age and bodyweight.
Effect of Hybrid Steel‐Basalt Fiber on Behaviors of Manufactured Sand RPC and Fiber Content Optimization Using Center Composite Design
Authors: Zhang Yunlong , Liu Jiahui , Wang Jing , Wu Bin
Published: December 2020

The mechanical properties and workability of manufactured sand reactive powder concrete (RPC) mixed with steel and basalt fibers were studied using the response surface method. The central composite design was used to explore the 7‐day and 28‐day compressive strength, flexural strength, and workability of different amounts of mixed fiber‐manufactured sand RPC. Results showed that when the steel fiber content was less than 2.5%, mixing basalt fibers can significantly improve the flexural strength and flexural‐compressive ratio of RPC. The relationship equations of the two fibers with the 28‐day compressive strength, flexural strength, and flexural‐compressive ratio of the manufactured sand RPC were obtained through the response surface model. The model proved to be reliable according to the analysis of variance. The content of the two fibers was optimized by multiobjective optimization technology, and the optimal content of the mixed fiber‐manufactured sand RPC under standard curing conditions was verified.
Analysis of Cusp Catastrophic Model for Vertical Stability of Drilling Shaft Lining
Authors: Liu Jimin , Cheng Hua , Rong Chuanxin , Wang Changbai
Published: December 2020

The vertical stability analysis of the drilling shaft lining has long been a technical problem in the construction of underground space development projects. And the critical depth of vertical stability was a key parameter to judge its stability. To determine this parameter, a simple and practical computational method would be helpful. In this paper, a new vertical stability analysis model of shaft lining structure based on catastrophe theory was proposed. In accordance with the mechanical analysis, the catastrophic instability mechanics was analyzed and a new critical depth of drilling shaft lining was deduced. Further, the rationality and feasibility of the catastrophic calculation model was proved by the numerical simulation results in a case. And the sensitivity of the influencing parameters was also analyzed, which provided theoretic reference for optimization design and guiding security construction. The results implied that catastrophic calculation model, as an alternative method for shaft stability analysis, could be applied to theoretical analysis and guiding engineering practice in the study of drilling shaft lining’s vertical stability.
ORAI2 Promotes Gastric Cancer Tumorigenicity and Metastasis through PI3K/Akt Signaling and MAPK-Dependent Focal Adhesion Disassembly
Authors: Wu Shayi , Chen Miao , Huang Jiao , Zhang Feifei , Lv Zhaojie , Jia Yongxu , Cui Yu-Zhu , Sun Liang-Zhan , Wang Ying , Tang Ying , Verhoeft Krista R. , Li Yan , Qin Yanru , Lin Xiang , Guan Xin-Yuan , Lam Ka-On
Published: December 2020

The ubiquitous second messenger Ca2+ has long been recognized as a key regulator in cell migration. Locally confined Ca2+, in particular, is essential for building front-to-rear Ca2+ gradient, which serves to maintain the morphologic polarity required in directionally migrating cells. However, little is known about the source of the Ca2+ and the mechanism by which they crosstalk between different signaling pathways in cancer cells. Here, we report that calcium release–activated calcium modulator 2 (ORAI2), a poorly characterized store-operated calcium (SOC) channel subunit, predominantly upregulated in the lymph node metastasis of gastric cancer, supports cell proliferation and migration. Clinical data reveal that a high frequency of ORAI2-positive cells in gastric cancer tissues significantly correlated with poor differentiation, invasion, lymph node metastasis, and worse prognosis. Gain- and loss-of-function showed that ORAI2 promotes cell motility, tumor formation, and metastasis in both gastric cancer cell lines and mice. Mechanistically, ORAI2 mediated SOC activity and regulated tumorigenic properties through the activation of the PI3K/Akt signaling pathways. Moreover, ORAI2 enhanced the metastatic ability of gastric cancer cells by inducing FAK-mediated MAPK/ERK activation and promoted focal adhesion disassembly at rear-edge of the cell. Collectively, our results demonstrate that ORAI2 is a novel gene that plays an important role in the tumorigenicity and metastasis of gastric cancer.

Significance:

These findings describe the critical role of ORAI2 in gastric cancer cell migration and tumor metastasis and uncover the translational potential to advance drug discovery along the ORAI2 signaling pathway.
Comparison of Adrenergic and Purinergic Receptor Contributions to Vasomotor Responses in Mesenteric Arteries of C57BL/6J Mice and Wistar Rats
Authors: Mittal Astha , Park Peter D. , Mitchell Ray , Fang Hanwei , Bagher Pooneh
Published: December 2020

Introduction: The sympathetic nervous system can modulate arteriolar tone through release of adenosine triphosphate and norepinephrine, which bind to purinergic and adrenergic receptors (ARs), respectively. The expression pattern of these receptors, as well as the composition of neurotransmitters released from perivascular nerves (PVNs), can vary both in organ systems within and across species, such as mice and rats. Objective: This study explores the function of α1A subtypes in mouse and rat third-order mesenteric arteries and investigates PVN-mediated vasoconstriction to identify which neurotransmitters are released from sympathetic PVNs. Methods: Third-order mesenteric arteries from male C57BL/6J mice and Wistar rats were isolated and mounted on a wire myograph for functional assessment. Arteries were exposed to phenylephrine (PE) and then incubated with either α1A antagonist RS100329 (RS) or α1D antagonist BMY7378, before reexposure to PE. Electrical field stimulation was performed by passing current through platinum electrodes positioned adjacent to arteries in the absence and presence of a nonspecific alpha AR blocker phentolamine and/or P2X1-specific purinergic receptor blocker NF449. Results: Inhibition of α1 ARs by RS revealed that PE-induced vasoconstriction is primarily mediated through α1A and that the contribution of the α1A AR is greater in rats than in mice. In the mouse model, sympathetic nerve-mediated vasoconstriction is mediated by both ARs and purinergic receptors, whereas in rats, vasoconstriction appeared to only be mediated by ARs and a nonpurinergic neurotransmitter. Further, neither model demonstrated that α1D ARs play a significant role in PE-mediated vasoconstriction. Conclusions: The mesenteric arteries of male C57BL/6J mice and Wistar rats have subtle differences in the signaling mechanisms used to mediate vasoconstriction. As signaling pathways in humans under physiological and pathophysiological conditions become better defined, the current study may inform animal model selection for preclinical studies.
Eosinophilic Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis
Authors: Ito Hiroyuki , Mishima Yusuke , Cho Tsubomi , Ogiwara Naoki , Shinma Yoshimasa , Yokota Masashi , Anzai Kazuya , Tsuda Shingo , Nagata Junko , Kojima Seiichiro , Sasaki Noriko , Wakabayashi Takayuki , Watanabe Norihito , Suzuki Takayoshi
Published: December 2020

We report a case of eosinophilic cholecystitis associated with eosinophilic granulomatosis with polyangiitis (EGPA) complicated by cerebral hemorrhage. A 60-year-old man presented to a local hospital with a diagnosis of acute cholecystitis, with persistent fever and epigastric pain for 2 weeks. His symptoms persisted despite 3-week hospitalization; therefore, he was transferred to our hospital for further evaluation. Laboratory investigations upon admission showed white blood cells 26,300/µL and significant eosinophilia (eosinophils 61%). Abdominal computed tomography revealed no gallbladder enlargement but a circumferentially edematous gallbladder wall. Additional blood test results were negative for antineutrophil cytoplasmic and perinuclear antineutrophil cytoplasmic antibodies; however, immunoglobulin (Ig)G and IgE levels were high at 1,953 mg/dL and 3,040/IU/mL, respectively. He improved following endoscopic transnasal gallbladder drainage for cholecystitis and was diagnosed with EGPA and received corticosteroid and immunosuppressant combination therapy. The eosinophil count decreased immediately after treatment, and abdominal pain and numbness resolved. He returned with left-sided suboccipital hemorrhage likely attributed to EGPA 6 months after discharge. EGPA is characterized by inflammation of small blood vessels and clinically manifests with an allergic presentation of bronchial asthma, as well as renal dysfunction, interstitial pneumonia, enteritis, and cerebral hemorrhage. Few reports have described cholecystitis as a presenting symptom of EGPA. We report a rare case of such a presentation with added considerations.
A Blueprint for Productive Maintenance of Certification, But Is the American Board of Internal Medicine up to the Challenge?
Authors: Alyesh Daniel , Gambhir Alok , Waase Marc , Remo Benjamin , Singh Abhijeet , Green Jacqueline , Kittleson Michelle , Estes N.A. Mark , Heist E. Kevin
Published: December 2020

The future of the American Board of Internal Medicine Maintenance of Certification (MOC) program is at a crossroads. The current MOC program lacks a clear visible mission, adds to modern health care’s onerous bureaucracy, and thus pulls physicians from the most important humanistic aspects of their profession. The aim of the MOC program should be to promote the best patient care by ensuring certified physicians maintain core skills through continuous education and evaluation. The program should focus on education and be designed with the rigorous obligations of practicing physicians in mind. Moving forward, the American Board of Internal Medicine should cocreate MOC with the physician community and apply innovative adult education techniques. Over time, data-driven methods and member feedback should be used to provide continuous program improvement. This review describes the origins of the current state of MOC, explores its evidence base, provides examples of model programs for the maintenance of complex professional skills, and outlines guiding principles for the future of MOC.
Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction
Authors: Zhao Hongmei , Yang Hongqin , Geng Chi , Chen Yang , Pang Junling , Shu Ting , Zhao Meijun , Tang Yaqin , Li Zhiwei , Li Baicun , Hou Cuiliu , Song Xiaomin , Wu Aoxue , Guo Xiaoxiao , Chen Si , Liu Bin , Yan Chen , Wang Jing
Published: December 2020

Background:

Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure are unknown.

Methods:

Serum IgE levels and cardiac FcεR1 expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone marrow transplantation. The roles of the IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes and cardiac fibroblasts (CFs). RNA sequencing and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1.

Results:

Serum IgE levels were significantly elevated in patients with heart failure as well as in 2 mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin II infusion. Interestingly, FcεR1 expression levels were also significantly upregulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated transverse aortic constriction– or angiotensin II–induced pathological cardiac remodeling or dysfunction. Anti-IgE antibodies (including the clinical drug omalizumab) also significantly alleviated angiotensin II–induced cardiac remodeling. Bone marrow transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non–bone marrow–derived cells. FcεR1 was found to be expressed in both cardiomyocytes and CFs. In cultured rat cardiomyocytes, IgE-induced cardiomyocyte hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA sequencing and signaling pathway analyses revealed that transforming growth factor-β may be a critical mediator, and blocking transforming growth factor-β indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro.

Conclusions:

Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in cardiomyocytes and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.
Risk of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Addition of SGLT2 Inhibitors Versus Sulfonylureas to Baseline GLP-1RA Therapy
Authors: Dave Chintan V. , Kim Seoyoung C. , Goldfine Allison B. , Glynn Robert J. , Tong Angela , Patorno Elisabetta
Published: December 2020

Background:

Several glucagon-like peptide receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefit in type 2 diabetes in large randomized controlled trials in patients with established cardiovascular disease or multiple risk factors. However, few trial participants were on both agents, and it remains unknown whether the addition of SGLT2i to GLP-1RA therapy has further cardiovascular benefits.

Methods:

Patients adding either SGLT2i or sulfonylureas to baseline GLP-1RA were identified within 3 US claims datasets (2013–2018) and were 1:1 propensity score–matched, adjusting for >95 baseline covariates. The primary outcomes were a composite cardiovascular end point (comprising myocardial infarction, stroke, and all-cause mortality) and heart failure hospitalization. Adjusted hazard ratios (HRs) and 95% CIs were estimated in each dataset and pooled through fixed-effects meta-analysis.

Results:

Among 12 584 propensity score–matched pairs (mean [SD] age, 58.3 [10.9] years; 48.2% male) across the 3 datasets, there were 107 composite cardiovascular end point events (incidence rate per 1000 person-years, 9.9 [95% CI, 8.1–11.9]) among SGLT2i initiators compared with 129 events (incidence rate, 13.0 [95% CI, 10.9–15.3]) among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.76 (95% CI, 0.59–0.98); this decrease in composite cardiovascular end point was driven by numeric decreases in the risk of myocardial infarction (HR, 0.71 [95% CI, 0.51–1.003]) and all-cause mortality (HR, 0.68 [95% CI, 0.40–1.14]) but not stroke (HR, 1.05 [95% CI, 0.62–1.79]). For the outcome of heart failure hospitalization, there were 141 events (incidence rate, 13.0 [95% CI, 11.0–15.2]) among SGLT2i initiators versus 206 events (incidence rate, 20.8 [95% CI, 18.1–23.8]) among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.65 (95% CI, 0.50–0.82).

Conclusions:

Risk of residual confounding cannot be fully excluded. Individual therapeutic agents within each class may have different magnitudes of effect. In this large real-world cohort of patients with diabetes already on GLP-1RA, addition of SGLT2i conferred greater cardiovascular benefit compared with addition of sulfonylurea. The magnitude of the cardiovascular risk reduction was comparable with the benefit seen in cardiovascular outcome trials of SGLT2i versus placebo, where baseline GLP-1RA use was minimal.
Which Imaging Approach Should Be Used for Stroke of Unknown Time of Onset?
Authors: Simonsen Claus Z. , Leslie-Mazwi Thabele M. , Thomalla Götz
Published: December 2020

Reperfusion therapy with intravenous thrombolysis or mechanical thrombectomy is effective in improving outcome for ischemic stroke but remains underused. Patients presenting with stroke of unknown onset are a common clinical scenario and a common reason for not offering reperfusion therapy. Recent studies have demonstrated the efficacy of reperfusion therapy in stroke of unknown time of onset, when guided by advanced brain imaging. However, translation into clinical practice is challenged by variability in the available data. Comparison between studies is difficult because of use of different imaging modalities (magnetic resonance imaging or computed tomography), different imaging paradigms (imaging biomarkers of lesion age versus imaging biomarkers of tissue viability), and different populations studied (ie, both patients with large vessel occlusion or those with less severe strokes). Physicians involved in acute stroke care are faced with the key question of which imaging approach they should use to guide reperfusion treatment for stroke with unknown time of onset. In this review, we provide an overview of the available evidence for selecting and treating patients with strokes of unknown onset, based on the underlying imaging concepts. The perspective provided is from the viewpoint of the clinician seeing these patients acutely, to provide pragmatic recommendations for clinical practice.
Trade Shocks, Firm Hierarchies, and Wage Inequality
Authors: Friedrich Benjamin U.
Published: December 2020

This paper shows robust effects of trade shocks on within-firm wage inequality through changes in firm hierarchies. It uses two distinct research designs—one considering firm-level shocks to foreign demand and transportation costs, the other analyzing the Muslim boycott of Danish exports after the 2006 “cartoon crisis.” Consistent with knowledge-based and incentive-based hierarchy models, trade shocks affect organizational choices through production scale. Adding a hierarchy layer increases inequality throughout the organization, particularly widening the 90-50 wage gap and pay differences between top and bottom layers. Delayering after the boycott leads to wage compression through wage cuts, demotions, and employee turnover.
Resource Discoveries, FDI Bonanzas, and Local Multipliers: Evidence from Mozambique
Authors: Toews Gerhard , Vézina Pierre-Louis
Published: December 2020

We show that giant and unpredictable oil and gas discoveries trigger FDI bonanzas. Across developing countries, we document a 56% increase in FDI in the two years following a giant discovery. These booms are driven by new projects in sectors such as manufacturing, retail, services, and construction. To assess the job creation effects of one such FDI bonanza in Mozambique, we combine concurrent waves of household surveys and firm censuses and estimate the local job multiplier of FDI. Our estimates suggest that for each new FDI job, an additional 4.4 jobs are created locally, 2.1 of which are formal jobs.
Mission and the Bottom Line: Performance Incentives in a Multigoal Organization
Authors: Giné Xavier , Mansuri Ghazala , Shrestha Slesh A.
Published: December 2020

We assess the role of monetary incentives in a mission-oriented organization by randomly assigning workers to one of two bonus schemes, incentivizing either the performance of a microcredit program (bottom line) or the empowerment of clients (mission). We find that the credit bonus improved credit-related outcomes but undermined the social mission, while the social bonus did not harm the bottom line. These results are consistent with a multitasking model with production spillovers or with prosocial behavior. We show that when mission-related rewards are not feasible, organizations that care about both the mission and the bottom line prefer flat wages to incentives.
Asymmetric Network Connectedness of Fears
Authors: Baruník Jozef , Bevilacqua Mattia , Tunaru Radu
Published: December 2020

This paper introduces forward-looking measures of the network connectedness of fears in the financial system arising due to the good and bad beliefs of market participants about uncertainty that spreads unequally across a network of banks. We argue that this asymmetric network structure extracted from call and put traded option prices of the main U.S. banks contains valuable information for predicting macroeconomic conditions and economic uncertainty, and it can serve as a tool for forward-looking systemic risk monitoring.
Long-Run Saving Dynamics: Evidence from Unexpected Inheritances
Authors: Druedahl Jeppe , Martinello Alessandro
Published: December 2020

We exploit inheritance episodes to provide novel causal evidence on the long-run effects of a large financial windfall on saving behavior. For identification, we combine a longitudinal panel of administrative wealth reports with variation in the timing of sudden, unexpected parental deaths. We show that after inheritance, net worth converges toward the path established before parental death, with only one-third of the initial windfall remaining after nine years. We interpret these findings through the lens of a generalized consumption-saving framework. To quantitatively replicate this behavior, life-cycle consumption models require impatient consumers and strong precautionary saving motives.
Testing the Water: Drinking Water Quality, Public Notification, and Child Outcomes
Authors: Marcus Michelle
Published: December 2020

Health-based drinking water violations affect about one in twelve Americans annually, yet the benefits of drinking water regulation are not well understood. I exploit plausibly exogenous variation in water quality violation timing to estimate the impacts on avoidance behavior and child outcomes. Using purchases of bottled water and common stomach remedies, emergency room visits for gastrointestinal illness, and school absences, I provide a comprehensive calculation of costs associated with poor drinking water quality. Individuals avoid the negative health impacts of coliform bacteria violations only when informed immediately. Timely public notification is a cost-effective way to induce avoidance behavior and protect health.
Time-Varying Risk Aversion? Evidence from Near-Miss Accidents
Authors: Shum Matthew , Xin Yi
Published: December 2020

We present evidence consistent with time-varying risk preferences among automobile drivers. Exploiting a unique data set of agents' high-frequency driving behavior collected by a mobile phone application, we show that drivers drive more conservatively following near-miss accidents. In a preferred specification, a near-miss triggers a reduction in driving distance of 12.98 kilometers, in-car cell phone use by more than 100%, and highway use by 43.24%. Structural estimation results indicate that such changes in behavior are consistent with an increase in risk aversion of 10.54% to 43.77% and a reduction in annual insurance cost amounting to 2.04% to 3.31% of the average car insurance premium.
Choice and Personal Responsibility: What Is a Morally Relevant Choice?
Authors: Cappelen Alexander W. , Fest Sebastian , Sørensen Erik Ø. , Tungodden Bertil
Published: December 2020

The principle that people should be held personally responsible for the consequences of their choices is a fundamental moral ideal in Western societies. We report from a large-scale experimental study of how far-reaching this principle is for inequality acceptance. We show that third-party spectators violate minimal conditions for a morally relevant choice when making redistributive decisions for two workers. They accept more inequality when the workers have made nominal and forced choices than when brute luck is the source of inequality. We argue that our findings shed light on important current political debates about personal responsibility and redistributive policies.
Racial Disparities in Voting Wait Times: Evidence from Smartphone Data
Authors: Chen M. Keith , Haggag Kareem , Pope Devin G. , Rohla Ryne
Published: December 2020

Equal access to voting is a core feature of democratic government. Using data from hundreds of thousands of smartphone users, we quantify a racial disparity in voting wait times across a nationwide sample of polling places during the 2016 U.S. presidential election. Relative to entirely white neighborhoods, residents of entirely black neighborhoods waited 29% longer to vote and were 74% more likely to spend more than thirty minutes at their polling place. This disparity holds when comparing predominantly white and black polling places within the same states and counties and survives numerous robustness and placebo tests. We shed light on the mechanism for these results and discuss how geospatial data can be an effective tool to measure and monitor these disparities going forward.
Aristotle on the Necessity of Habituation
Authors: Hampson Margaret
Published: December 2020

In Nicomachean Ethics 2.4 Aristotle raises a puzzle about moral habituation. Scholars take the puzzle to concern how a learner could perform virtuous actions, given the assumption that virtue is prior to virtuous action. I argue, instead, that Aristotle is concerned to defend the necessity of practice, given the assumption that virtue is reducible to virtuous action.
Picturing the Square, Streets, and Denizens of Early Modern Istanbul: Practices of Urban Space and Shifts in Visuality
Authors: Kafescioğlu Çiğdem
Published: December 2020

Exploring intersections of spaces, practices, and representations of urbanity and the city in late sixteenth-century Istanbul, this paper traces the emergence of a new set of themes centered on the main public square, the streets, and the denizens of the Ottoman capital in illustrated court histories. It considers new visual imaginings of city and urbanity in view of three issues that resonate with the history of early modern Istanbul: modalities and the lexicon of vision as they took shape parallel to changing spatial practices; the making of a new urban public, and polyphonic forms of representation concomitant to the emergence of new publicities; the conflicted political environment that turned the city’s public spaces into arenas of contestation in the later decades of the 1500s. To this end, the article focuses on narrative paintings and texts of a set of manuscripts created between the late 1580s and the turn of the seventeenth century, and with particular attention to the Sūrnāme-i Humāyūn (Book of Festivities, 1588), explores the notions and connections that shaped them.
A Seminal Event
Authors: O’Leary Joseph S.
Published: December 2020

In this article, Joseph S. O’Leary recounts the origin and inspirations behind the 1979 Colloquium Heidegger et la Question de Dieu, and reflects on why it became such a key moment in the development of many of those who took part in it. In addition to the contingent factors of a particular time and place, and the deep personal and intellectual significance that Heidegger bore for many of them, O’Leary identifies the perennial philosophical questions which the participants were able to address in original and controversial ways. O’Leary also reflects on the way this Colloquium served as a subsequent influence on his own original work as well as the critical dialogue he engaged in with many of the other participants, culminating in his most recent work on interreligious dialogue which further amplifies the central problematics here concerning the nature of the quest for truth.
Thinking God in France
Authors: Littlejohn M.E. , Rumpza Stephanie
Published: December 2020

Organized by Richard Kearney and Joseph S. O’Leary, the 1979 Colloquium Heidegger et la question de Dieu was of critical importance for the development of phenomenology of religion in France. This special issue introduces the event and its ensuing publication to the English-speaking world. The editors’ historical and thematic contextualizing essay is followed by contributions from six leading philosophers. Richard Kearney sets the stage by updating his original foreword, while Jean-Yves Lacoste presents the central moments in the history of Heidegger’s complicated relationship to Christian thinking. Paul Ricoeur’s “Introductory Note” delivers a well-known challenge to Heidegger in a piece whose brevity belies its impact. Finally, three participants of the 1979 Colloquium, Joseph S. O’Leary, Jean Greisch, and Jean-Luc Marion, reflect back on the significance of this event and its role in developing their own groundbreaking work. The special issue closes with a brief reflection on where we find ourselves in philosophy today.