bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytic Solutions and Stability of Sixth Order Difference Equations
Authors: Alayachi H. S. , Noorani M. S. M. , Khan A. Q. , Almatrafi M. B.
Published: September 2020

In the present paper, the global attractor, local stability, and boundedness of the solution of sixth order difference equations are investigated analytically and numerically. The exact solutions of three equations are presented by utilizing Fibonacci sequence. We also analyse the periodicity of a sixth order difference equation. The considered difference equations are given by yn+1=Ayn−1±Byn−1yn−3/Cyn−3±Dyn−5, n=0,1,…, where the initial conditions y−5,y−4,y−3,y−2,y−1, and y0 are arbitrary real numbers and the values A,B,C, and D are defined as positive real numbers.
Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer
Authors: Han Chenglin , Wang Zilong , Xu Yingkun , Chen Shuxiao , Han Yuqing , Li Lin , Wang Muwen , Jin Xunbo
Published: September 2020

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by‐product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.
Is It the pH That Matters? Challenging the Pathophysiology of Acidemia in a Case of Severe Hypercapnia Secondary to Intraoperative CO2 Insufflation
Authors: Merle Evan , Zaatari Saad , Spiegel Rory , Bahloul Mabrouk
Published: September 2020

Background. Acidemia has been long thought to lead to hemodynamic compromise. While some literature to date challenges this idea, there is no consensus on this topic. Case Summary. To our knowledge, this is the most severe case of hypercapnia and acidosis due to carbon dioxide (CO2) insufflation during laparoscopy reported in the literature. Remarkably, this patient remained hemodynamically normal despite having a blood pH below 6.81. This prompts a wider discussion about the effects of blood pH on human physiology. Most patients who present acidotic are critically ill and have confounding underlying metabolic or respiratory pathophysiology driving their illness. In this case, the patient experienced no respiratory insult leading to an increase in blood CO2 but rather had CO2 iatrogenically introduced into the circulatory system, effectively detaching the deleterious effects of CO2 from the respiratory pathologies that so often cause its accumulation. Conclusion. This raises the question, in patients with severe acidosis and hemodynamic compromise, is acidosis a symptom of the underlying process, or is the acidosis itself causing harm?
Efficacy and Safety of First-Line Immunotherapy in Combination with Chemotherapy for Patients with Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis
Authors: Wang Bi-Cheng , Xiao Bo-Ya , Li Peng-Cheng , Kuang Bo-Hua , Chen Wang-Bing , Li Pin-Dong , Lin Guo-He , Liu Quentin , You San Lin
Published: September 2020

Background. The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial. Objective. To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC. Methods. PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results. We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.93; risk ratio (RR) 0.90, 95% CI 0.81–1.00) and PFS (HR: 0.81, 95% CI 0.74–0.88; RR 0.96, 95% CI 0.93–0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%). Conclusion. In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.
Clinical Analysis of the Curative Effect of a Transnasal Ileus Tube in the Treatment of Small Bowel Obstruction Caused by a Phytobezoar
Authors: Lin Yong-Xu , Wang Sun-Jian , Liang Hui-Shun , Lin Su , Bian Li-Yong , Ding Jian , Li Dan , Mart n Venegas Raquel
Published: September 2020

Objective. To investigate the curative effect of a transnasal ileus tube in the treatment of small bowel obstruction caused by a phytobezoar. Methods. Seventy-one patients with small bowel obstruction caused by a phytobezoar who underwent treatment in three provincial tertiary grade A hospitals in Fujian Province from March 2011 to February 2020 were included in this study. Patients were divided into the following two groups according to the treatment received: (1) conservative group, comprising patients who received medical conservative treatment, and (2) combined group, including patients who received combined medical conservative treatment and transnasal ileus tube placement. The clinical symptoms, changes in abdominal imaging, tube depth of the first day, reduction of pressure volume on the first day after catheterization, length of hospital stay, and nonsurgical rate were compared between the combined and conservative groups. Results. There was no significant difference in age, sex, history of previous abdominal surgery and abdominal radiotherapy, symptoms at admission, duration of symptoms before admission, signs at admission, laboratory data, and obstruction position between the combined and conservative groups. There was a statistically significant difference in the nonsurgical rate (19/24 vs. 23/47,

P
=
0.014

) between the combined and conservative groups. Logistic analysis showed that the duration of symptoms before admission, albumin level, and use of a transnasal ileus tube might be independent factors affecting the transition to surgery for patients with small bowel obstruction caused by a phytobezoar (

P
<
0.05

). Conclusion. Timely conservative medical treatment with transnasal ileus tube placement can effectively improve the nonsurgical rate of small bowel obstruction caused by a phytobezoar. The duration of symptoms before admission, albumin level, and use of a transnasal ileus tube were closely related to whether patients with small bowel obstruction caused by phytobezoar were transferred to surgery.
Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease
Authors: Wi Rayul , Chung Young Cheul , Jin Byung Kwan , Duan Lihua
Published: September 2020

The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. RT-PCR analysis shows the upregulation of inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α in microglia in the SN in vivo, indicating the activation of the inflammatory system. By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. Capsaicin neuroprotection is accompanied by inhibiting MPTP-induced glial activation and production of inflammatory cytokines. Treatment with AM251 and AM630 (CB1/2 antagonists) abolished capsaicin-induced beneficial effects, indicating the existence of a functional crosstalk between CB and TRPV1. Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. These results suggest that the cannabinoid and vanilloid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with neuroinflammation.
A Privacy Risk Assessment Model for Medical Big Data Based on Adaptive Neuro-Fuzzy Theory
Authors: Shi Mingyue , Jiang Rong , Zhou Wei , Liu Sen , Sciancalepore Savio
Published: September 2020

Information leakage in the medical industry has become an urgent problem to be solved in the field of Internet security. However, due to the need for automated or semiautomated authorization management for privacy protection in the big data environment, the traditional privacy protection model cannot adapt to this complex open environment. Although some scholars have studied the risk assessment model of privacy disclosure in the medical big data environment, it is still in the initial stage of exploration. This paper analyzes the key indicators that affect medical big data security and privacy leakage, including user access behavior and trust, from the perspective of users through literature review and expert consultation. Also, based on the user’s historical access information and interaction records, the user’s access behavior and trust are quantified with the help of information entropy and probability, and a definition expression is given explicitly. Finally, the entire experimental process and specific operations are introduced in three aspects: the experimental environment, the experimental data, and the experimental process, and then, the predicted results of the model are compared with the actual output through the 10-fold cross verification with Matlab. The results prove that the model in this paper is feasible. In addition, the method in this paper is compared with the current more classical medical big data risk assessment model, and the results show that when the proportion of illegal users is less than 15%, the model in this paper is more superior in terms of accuracy and recall.
Spatial Information and Performance Evaluation in Coprime Array
Authors: Zhou Ying , Xu Dazhuan , Shi Chao , Tu Weilin , Shi Junpeng
Published: September 2020

In this paper, the mutual information between the received signals and the source in the coprime linear array is investigated. In Shannon’s information theory, the mutual information is used to quantify the reduction in the priori uncertainty of the transmitted message. Similarly, the spatial information in the coprime array is the mutual information between direction of arrival (DOA), source amplitude, and received signals. Such information content is composed of two parts. The first part is DOA information, and the second one is scattering information. In a single source scenario, we derive the theoretical expression and its asymptotic upper bound of DOA information. The corresponding expression of scattering information is also formulated theoretically. Besides, the application of spatial information is discussed. We can obtain the optimal array configuration by maximizing the DOA information of the coprime array. Similarly, the information is also used to quantify the performance difference between the coprime array and uniform array. In addition, the entropy error is employed to evaluate the estimation performance based on spatial information. Numerical simulation of the information content confirms our theoretical analysis. The results in this paper have important guiding significance for the design of the coprime array in the actual environment.
An Improved Prediction Model Combining Inverse Exponential Smoothing and Markov Chain
Authors: Niu Tong , Zhang Lin , Zhang Bo , Yang Bofan , Wei Shengjun , Manfredi Paolo
Published: September 2020

On the basis of the triple exponential smoothing prediction model, this paper introduces the reverse prediction idea and establishes the reverse triple exponential smoothing model by setting parameters such as threshold value and iteration times and reasonably correcting its initial value. This method can effectively reduce the error of early prediction value. At the same time, aiming at the problem that the predicting advantage of the reverse triple exponential smoothing model weakens in the later period, Markov theory is introduced to correct its error value, and an improved prediction model combining inverse exponential smoothing and Markov chain is further established. The improved model combines the advantages of index model trend prediction and Markov fluctuation prediction, and the prediction accuracy and stability of the model are significantly improved through case tests.
Antagonistic Effects of Tetramethylpyrazine on Hypoxic Respiratory Depression in Rats
Authors: Li Li , Gao Bo , Liu Meifang
Published: September 2020

Objective. Tetramethylpyrazine (TMP) is an alkaloid extracted from the root and stem of the traditional Chinese herbal medicine called Chuanxiong. The present study aims to study the effects of TMP on hypoxic respiratory depression in rats. Materials and methods. The effects of TMP on respiratory responses of rats induced by hypoxia were observed by diaphragm electromyogram (EMG) recording. The effects of TMP on the protein expression of FOS and acid sensing ion channel1a (ASIC1a) in the brainstem induced by hypoxia were investigated by immunohistochemistry. Results. The respiration of rats was first excited and then depressed during hypoxia treatment, while TMP pretreatment could significantly antagonize the respiratory depression induced by hypoxia (P < 0.01). Hypoxia obviously induced the protein expression of FOS (P < 0.01) and ASIC1a(P < 0.05) in the brainstem, which can be also significantly inhibited by TMP pretreatment. Conclusions. TMP has protective effects on hypoxic respiratory depression, and the mechanisms might be concerned with its downregulation of FOS and ASIC1a in the brainstem induced by hypoxia.
Measurement Matrix Optimization via Mutual Coherence Minimization for Compressively Sensed Signals Reconstruction
Authors: Wei Ziran , Zhang Jianlin , Xu Zhiyong , Liu Yong , Okarma Krzysztof
Published: September 2020

For signals reconstruction based on compressive sensing, to reconstruct signals of higher accuracy with lower compression rates, it is required that there is a smaller mutual coherence between the measurement matrix and the sparsifying matrix. Mutual coherence between the measurement matrix and sparsifying matrix can be expressed indirectly by the property of the Gram matrix. On the basis of the Gram matrix, a new optimization algorithm of acquiring a measurement matrix has been proposed in this paper. Firstly, a new mathematical model is designed and a new method of initializing measurement matrix is adopted to optimize the measurement matrix. Then, the loss function of the new algorithm model is solved by the gradient projection-based method of Gram matrix approximating an identity matrix. Finally, the optimized measurement matrix is generated by minimizing mutual coherence between measurement matrix and sparsifying matrix. Compared with the conventional measurement matrices and the traditional optimization methods, the proposed new algorithm effectively improves the performance of optimized measurement matrices in reconstructing one-dimensional sparse signals and two-dimensional image signals that are not sparse. The superior performance of the proposed method in this paper has been fully tested and verified by a large number of experiments.
Existence of Mild Solutions for a Class of Impulsive Hilfer Fractional Coupled Systems
Authors: Guida Karim , Hilal Khalid , Ibnelazyz Lahcen , Mei Ming
Published: September 2020

The aim of this paper is to give existence results for a class of coupled systems of fractional integrodifferential equations with Hilfer fractional derivative in Banach spaces. We first give some definitions, namely the Hilfer fractional derivative and the Hausdorff’s measure of noncompactness and the Sadovskii’s fixed point theorem.
Photosensitive Epilepsy and Polycystic Ovary Syndrome as Manifestations of MERRF
Authors: Finsterer Josef , Berlit Peter
Published: September 2020

Objectives. Although endocrinologic involvement and epilepsy are frequent features of myoclonic epilepsy with ragged-red fibers (MERRF), polycystic ovary syndrome (PCOS) and photosensitive epilepsy have not been reported. Case Report. A 32-year-old female was diagnosed with MERRF at age 19 y upon presence of the four canonical features and the variant m.8344A > G in MT-TK (tRNA (Lys)) (blood heteroplasmy rate: 50%). She experienced recurrent photosensitive focal and generalised seizures since age 19 y, which could be triggered by flickering light or by looking at small stones, leaves, or dirty snow on the ground. Since the last 42 months, she was seizure-free upon levetiracetam (4000 mg/d), clonazepam (1.5 mg/d), and topiramate (25 mg/d). Additionally, she suffered from secondary amenorrhoea since adolescence. She was married between ages 19 y and 25 y but did not get pregnant. PCOS was diagnosed and treated with desogestrel plus estradiol. Nonetheless, the course was progressive, particularly with regard to ataxia, myocloni, and myopathy. Conclusions. The phenotypic spectrum of MERRF is broader than anticipated and may additionally include PCOS and photosensitive epilepsy. PCOS in MERRF may respond to hormone substitution and photosensitive epilepsy to levetiracetam, clonazepam, and topiramate.
Discovering Associations: Kawasaki Disease and COVID-19
Authors: Peterson Nicholas , Sagdeo Kaustubh , Tyungu Donna , Harper Cristin , Mihaylo Kyle , Pollak-Christian Elza , Takaya Junji
Published: September 2020

The COVID-19 pandemic has resulted in over 3.6 million confirmed cases and over 254,000 deaths worldwide. It has been theorized that children who are asymptomatic or who do not display significant respiratory symptoms are potential vectors for community transmission of the SARS-CoV-2 virus. This is incompletely understood due to the current lack of widespread testing in the pediatric population. We describe a case of a 2-year-old female who presented with symptoms of prolonged fever, conjunctivitis, extremity edema, rash, dry/cracked lips, fussiness and fatigue, and a notable absence of respiratory symptoms. She was diagnosed with and treated for Kawasaki disease. Due to her prolonged fever, she was tested for COVID-19 which was positive; however, she did not develop respiratory symptoms during her illness. At the time of manuscript submission, this is the second case report to our knowledge showing an association between Kawasaki Disease and SARS-CoV-2 virus, both of which are poorly understood diseases in the pediatric population. This case highlights the value of testing pediatric patients for COVID-19 who present with fever in the absence of other symptoms to improve epidemiologic measures during the ongoing pandemic, and it also adds to a foundation of cases for future research on the presence of a link between Kawasaki Disease and COVID-19.
The Efficacy of Linked Color Imaging in the Endoscopic Diagnosis of Barrett’s Esophagus and Esophageal Adenocarcinoma
Authors: Tokunaga Mamoru , Matsumura Tomoaki , Ishikawa Kentaro , Kaneko Tatsuya , Oura Hirotaka , Ishikawa Tsubasa , Nagashima Ariki , Shiratori Wataru , Okimoto Kenichiro , Akizue Naoki , Maruoka Daisuke , Ohta Yuki , Saito Keiko , Nakagawa Tomoo , Chiba Tetsuhiro , Arai Makoto , Kato Jun , Kato Naoya , Brunetti Oronzo
Published: September 2020

Background. The present study aimed to evaluate the efficacy of linked color imaging (LCI) in diagnosing Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Methods. A total of 112 and 12 consecutive patients with BE and EAC were analyzed. The visibility scores of BE and EAC ranging from 4 (excellent visibility) to 0 (not detectable) were evaluated by three trainees and three experts using white light imaging (WLI), LCI mode, and blue laser imaging bright (BLI-b) mode. In addition,

L
∗
a
∗
b
∗

color values and color differences (

Δ
E
∗

) were evaluated using the CIELAB color space system. Results. The visibility score of the BE in LCI mode (

2.94
±
1.32

) was significantly higher than those in WLI (

2.46
±
1.48

) and BLI-b mode (

2.35
±
1.46

) (

p
<
0.01

). The color difference (

Δ
E
∗

) from the adjacent gastric mucosa in LCI mode (

17.11
±
8.53

) was significantly higher than those in other modes (

12.52
±
9.37

in WLI and

11.96
±
6.59

in BLI-b mode,

p
<
0.01

). The visibility scores of EAC in LCI mode (

2.56
±
1.47

) and BLI-b mode (

2.51
±
1.28

) were significantly higher than that in WLI (

1.64
±
1.46

) (

p
<
0.01

). The color difference (

Δ
E
∗

) from the adjacent normal Barrett’s mucosa in LCI mode (

19.96
±
7.97

) was significantly higher than that in WLI (

12.95
±
11.86

) (

p
=
0.03

). Conclusion. The present findings suggest that LCI increases the visibility of BE and EAC and contributes to the improvement of the detection of these lesions.
Autoantibodies in Early Detection of Breast Cancer
Authors: Rauf Femina , Anderson Karen S. , LaBaer Joshua
Published: September 2020

In spite of the progress made in treatment and early diagnosis, breast cancer remains a major public health issue worldwide. Although modern image-based screening modalities have significantly improved early diagnosis, around 15% to 20% of breast cancers still go undetected. In underdeveloped countries, lack of resources and cost concerns prevent implementing mammography for routine screening. Noninvasive, low-cost, blood-based markers for early breast cancer diagnosis would be an invaluable alternative that would complement mammography screening. Tumor-specific autoantibodies are excellent biosensors that could be exploited to monitor disease-specific changes years before disease onset. Although clinically informative autoantibody markers for early breast cancer screening have yet to emerge, progress has been made in the development of tools to discover and validate promising autoantibody signatures. This review focuses on the current progress toward the development of autoantibody-based early screening markers for breast cancer.

See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”
Phase I Trial of Debio 1143, an Antagonist of Inhibitor of Apoptosis Proteins, Combined with Cisplatin Chemoradiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Le Tourneau Christophe , Tao Yungan , Gomez-Roca Carlos , Cristina Valerie , Borcoman Edith , Deutsch Eric , Bahleda Rastislav , Calugaru Valentin , Modesto Anouchka , Rouits Elisabeth , Gollmer Kathrin , Vuagniaux Gregoire , Crompton Philippa , Zanna Claudio , Szyldergemajn Sergio , Delord Jean-Pierre , Bourhis Jean
Published: September 2020

Purpose:

Debio 1143 is an oral antagonist of inhibitor of apoptosis proteins, which enhances tumor response with concomitant chemoradiotherapy. Addition of Debio 1143 to cisplatin-based chemoradiotherapy in locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN) was evaluated in a phase I/II study to determine the MTD and recommended phase II dose (RP2D). Here, phase I results are reported.

Patients and Methods:

Treatment-naïve patients with LA-SCCHN (stages III/IVA/IVB) received Debio 1143 (100, 200, 300 mg/day), for 14 days every 3 weeks, with cisplatin (100 mg/m², every 3 weeks), for three cycles, and concomitant conventional fractionation radiotherapy (70 Gy/7 weeks). Dose-limiting toxicity (DLT) was evaluated over 9 weeks using continual reassessment.

Results:

Fourteen patients were treated/evaluable for DLT. Median age was 64.5 years, and all patients were current/former smokers. Primary tumors were hypopharynx, oropharynx (all human papillomavirus/p16 negative), larynx, and oral cavity. Two of six patients at 200 mg/day had DLT (grade 3 tubular necrosis, grade 3 aspartate aminotransferase/alanine aminotransferase increase, grade 4 febrile neutropenia, and grade 3 lipase increase), which was considered the MTD and RP2D. Common grade 3–4 adverse events were dysphagia (36%) and mucositis (29%). Laboratory abnormalities were frequent and generally mild, including anemia, white blood cell decrease, and increased creatinine. Addition of Debio 1143 did not compromise chemotherapy administration. Overall locoregional control rate at 18 months was 85%. Overall response rate was 85%, including 69% complete responses. Progression-free survival rate at 24 months was 74%.

Conclusions:

The RP2D of Debio 1143 is 200 mg/day for 14 days, every 3 weeks, when combined with concomitant high-dose cisplatin chemoradiotherapy in LA-SCCHN. Debio 1143 addition to chemoradiotherapy was safe and manageable. Preliminary efficacy is encouraging and supports further development.
Aromatase Inhibitors in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer: Profiles of Psychological Symptoms and Quality of Life in Different Patient Clusters
Authors: Borreani Claudia , Alfieri Sara , Infante Gabriele , Miceli Rosalba , Mariani Paola , Bosisio Marco , Vernieri Claudio , Bianchi Giulia V. , Capri Giuseppe
Published: September 2020

Background: Aromatase inhibitors (AIs) as adjuvant therapy after breast cancer (BC) surgery have demonstrated to reduce the risk of disease recurrence, to lower the risk of contralateral BC, and to improve survival when compared to tamoxifen in patients with limited-stage hormone receptor-positive (HR+) BC. However, AIs are associated with adverse events that can have a significant impact on patient quality of life (QoL). Aim: This study aimed to identify profiles of psychological symptoms and QoL in HR+ BC patients undergoing AI therapy. Method: Data were collected with questionnaires administered at three time points: AI initiation (t0); 3 months after AI initiation (t1); and 6 months after AI initiation (t2). The FACT-G, FACT-B, and FACT-ES questionnaires were used to assess QoL; psychological symptoms were assessed using the SCL-90-R. Results: 43 women were enrolled in the study (t0), and 37 completed the t1 evaluation and 29 the t2 evaluation. We found (1) a progressive decrease over time in FACT-G and FACT-ES scores, in particular in the Physical, Emotional, and Endocrine subscales, and an increase in the SOM (somatization) subscale of the SCL-90-R; (2) the presence of 4 clusters related to different psychological symptoms and QoL evolution over time; (3) that patients belonging to the cluster characterized by worsening symptoms and QoL during time differed from the others in the Emotional subscale of the FACT-B and in the GSI (Global Score), OCD (obsessive-compulsive), DEP (depression), ANX (anxiety), and SLP (sleep disorders) dimensions of the SCL-90-R and had significantly higher BMI levels; and (4) that 3 items from the SCL-90-R and 2 items from FACT Emotional Well-Being subscale were predictive of the “worst” cluster. Conclusions: Although larger studies are needed to confirm these results, our data open up new ways of investigation into the effects of AIs on QoL in HR+ BC patients.
Using Data from a Sickness Fund Claims Database to Assess the Treatment Patterns and Healthcare Resource Utilization among Patients with Metastatic Renal Cell Carcinoma in Germany
Authors: Bögemann Martin , Zagorska Aleksandra , Akumo Divine , Hadad Laila El , Pignot Marc
Published: September 2020

Objectives: To characterize real-world prescribing patterns and their clinical and healthcare resource utilization (HRU) implications in patients with metastatic renal cell carcinoma (mRCC) treated in Germany. Methods: Eligible individuals were enrolled in the “Bundesverband der Betriebskrankenkassen” claims database and received targeted mRCC therapy between 1 January 2008 and 31 December 2016. Prescribing patterns and HRU were characterized by treatment line and summarized by descriptive statistics. Proxy progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier curves. Results: 536 patients receiving mRCC treatment were included. The median treatment duration was 4.2 months (interquartile range [IQR]: 1.7–9.3) for first-line therapy and 3.8 months (IQR: 1.7–9.1) for second-line therapy. Median PFS and OS estimates were similar for the first- and second-line treatments: PFS, 7.4 versus 7.2 months; OS, 14.9 versus 13.6 months. Mean HRU costs were higher for patients receiving first-line therapy (€7,253.2) compared with those receiving second-line therapy (€6,242.9). Exploratory stratification of outcomes by centre expertise suggested a possible trend towards improved OS in the 10 most experienced centres versus all -others: first-line, 18.4 versus 13.2 months; second-line, 16.4 versus 12.4 months. Conclusions: In routine care, German clinicians make rational prescribing decisions; possible variations in outcomes between centres warrant further investigation.
Diabetic macular oedema: structural and functional results of sequential dexamethasone and aflibercept therapy after one year of treatment
Authors: Di Carlo Emiliano
Published: September 2020

Objective: The aim of this paper is to compare intravitreous aflibercept versus dexamethasone implant followed by aflibercept (sequential treatment group) in patients with diabetic macular edema (DME). Methods: We conducted an observational retrospective study in naïve DME patients, 15 treated only with aflibercept (a monthly injection for the first 5 consecutive doses, followed by an injection every 2 months), and 15 treated with a single dexamethasone implant followed by bimonthly aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and qualitative features as well as adverse events were assessed at baseline and at 2, 6, and 12 months. Results: BCVA increased from 70.8 ± 4.1 to 83.5 ± 2.7 letters with aflibercept and from 75.6 ± 2.7 to 86.5 ± 2.5 with sequential treatment (p = 0.551). CMT decreased from 411 ± 26.1 to 288.1 ± 10.5 with aflibercept and from 411.4 ± 24.3 to 260.8 ± 17.9 in the sequential treatment group. The differences between the 2 groups, in terms of visual gain and decreased MT, were not statistically significant (p > 0.05). Nine and 6 injections and 9 and 7 monitoring visits were performed. Conclusion: Sequential treatment in DME, starting with dexamethasone and followed by aflibercept, is a promising alternative that can reduce the treatment burden in the first year without statistically significant differences in terms of visual gain and decreased MT compared to aflibercept only.
Prognostic factors for visual acuity in pseudophakic patients with epiretinal gliosis and macular surgery
Authors: Treder Maximilian
Published: September 2020

Purpose: To evaluate the visual prognostic factors in patients with pseudophakic epiretinal membrane (ERM) after vitrectomy using spectral domain optical coherence tomography (SD-OCT). Methods: A retrospective review of patients with pseudophakic ERM having undergone vitrectomy was conducted. Best corrected visual acuity (BCVA) and SD-OCT were conducted before and 1, 3, and 6 months after vitrectomy. Known visual prognostic factors, such as inner-retina irregularity index, central foveal thickness (CFT), central inner retinal layer thickness (CIRLT), cone outer segment tip defect length, and photoreceptor outer segment length, were reviewed and their correlation with BCVA was analyzed. Results: Forty-three patients (mean age: 64.88 ± 10.46 years) with pseudophakic ERM were included. BCVA significantly improved after vitrectomy (logMAR 0.30 ± 0.24 vs. 0.11 ± 0.14, p < 0.001). The preoperative high inner-retina irregularity index significantly correlated with poor postoperative BCVA in patients with pseudophakic ERM (correlation coefficient 0.583, p < 0.001). Postoperative improvements of inner retinal SD-OCT findings, such as innerretina irregularity index, CFT, and CIRLT, were significantly associated with the amount of BCVA improvement after ERM surgery (correlation coefficients were as follows: inner-retina irregularity index – 0.711, p < 0.001; CFT – 0.462, p = 0.002; CIRLT – 0.596, p < 0.001). However, preoperative outer retinal SD-OCT findings were not associated with postoperative visual prognosis. Conclusion: From this study, we determined the visual prognostic factors of ERM surgery without confounding factors, such as visual acuity improvement following combined cataract surgery, and inner retinal SD-OCT findings more significantly associated with the visual prognosis of ERM surgery compared to outer retinal SD-OCT findings.
Multidisciplinary Cardiac Rehabilitation and Long-Term Prognosis in Patients With Heart Failure
Authors: Kamiya Kentaro , Sato Yukihito , Takahashi Tetsuya , Tsuchihashi-Makaya Miyuki , Kotooka Norihiko , Ikegame Toshimi , Takura Tomoyuki , Yamamoto Takanobu , Nagayama Masatoshi , Goto Yoichi , Makita Shigeru , Isobe Mitsuaki
Published: September 2020

Background:

Exercise-based cardiac rehabilitation (CR) improves health-related quality of life and exercise capacity in patients with heart failure (HF). However, CR efficacy in patients with HF who are elderly, frail, or have HF with preserved ejection fraction remains unclear. We examined whether participation in multidisciplinary outpatient CR is associated with long-term survival and rehospitalization in patients with HF, with subgroup analysis by age, sex, comorbidities, frailty, and HF with preserved ejection fraction.

Methods:

This multicenter retrospective cohort study was performed in patients hospitalized for acute HF at 15 hospitals in Japan, 2007 to 2016. The primary outcome (composite of all-cause mortality and HF rehospitalization after discharge) and secondary outcomes (all-cause mortality and HF rehospitalization) were analyzed in outpatient CR program participants versus nonparticipants.

Results:

Of the 3277 patients, 26% (862) participated in outpatient CR. After propensity matching for potential confounders, 1592 patients were included (n=796 pairs), of which 511 had composite outcomes (223 [14%] all-cause deaths and 392 [25%] HF rehospitalizations, median 2.4-year follow-up). Hazard ratios associated with CR participation were 0.77 (95% CI, 0.65–0.92) for composite outcome, 0.67 (95% CI, 0.51–0.87) for all-cause mortality, and 0.82 (95% CI, 0.67–0.99) for HF-related rehospitalization. CR participation was also associated with numerically lower rates of composite outcome in patients with HF with preserved ejection fraction or frail patients.

Conclusions:

Outpatient CR participation was associated with substantial prognostic benefit in a large HF cohort regardless of age, sex, comorbidities, frailty, and HF with preserved ejection fraction.
PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36
Authors: Qi Zhiyong , Hu Liang , Zhang Jianjun , Yang Wenlong , Liu Xin , Jia Daile , Yao Zhifeng , Chang Lin , Pan Guanxing , Zhong Haoxuan , Luo Xinping , Yao Kang , Sun Aijun , Qian Juying , Ding Zhongren , Ge Junbo
Published: September 2020

Background:

PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear.

Methods:

We detected the direct effects of PCSK9 on agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, α-granule release, spreading, and clot retraction. These studies were complemented by in vivo analysis of FeCl
3
-injured mouse mesenteric arteriole thrombosis. We also investigated the underlying mechanisms. Using the myocardial infarction (MI) model, we explored the effects of PCSK9 on microvascular obstruction and infarct expansion post-MI.

Results:

PCSK9 directly enhances agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, P-selectin release from α-granules, spreading, and clot retraction. In line, PCSK9 enhances in vivo thrombosis in a FeCl
3
-injured mesenteric arteriole thrombosis mouse model, whereas PCSK9 inhibitor evolocumab ameliorates its enhancing effects. Mechanism studies revealed that PCSK9 binds to platelet CD36 and thus activates Src kinase and MAPK (mitogen-activated protein kinase)–extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase, increases the generation of reactive oxygen species, and activates the p38MAPK/cytosolic phospholipase A2/cyclooxygenase-1/thromboxane A
2
signaling pathways downstream of CD36 to enhance platelet activation, as well. Using CD36 knockout mice, we showed that the enhancing effects of PCSK9 on platelet activation are CD36 dependent. It is important to note that aspirin consistently abolishes the enhancing effects of PCSK9 on platelet activation and in vivo thrombosis. Last, we showed that PCSK9 activating platelet CD36 aggravates microvascular obstruction and promotes MI expansion post-MI.

Conclusions:

PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis, and MI expansion post-MI, as well, by binding to platelet CD36 and thus activating the downstream signaling pathways. PCSK9 inhibitors or aspirin abolish the enhancing effects of PCSK9, supporting the use of aspirin in patients with high plasma PCSK9 levels in addition to PCSK9 inhibitors to prevent thrombotic complications.
Endothelial Cell Cystathionine γ‐Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury
Authors: Xia Huijing , Li Zhen , Sharp Thomas E. , Polhemus David J. , Carnal Jean , Moles Karl H. , Tao Ya‐Xiong , Elrod John , Pfeilschifter Josef , Beck Karl‐Friedrich , Lefer David J.
Published: September 2020

Background

Hydrogen sulfide (H
2
S) is an important endogenous physiological signaling molecule and exerts protective properties in the cardiovascular system. Cystathionine γ‐lyase (CSE), 1 of 3 H
2
S producing enzyme, is predominantly localized in the vascular endothelium. However, the regulation of CSE in vascular endothelium remains incompletely understood.

Methods and Results

We generated inducible endothelial cell‐specific CSE overexpressed transgenic mice (EC‐CSE Tg) and endothelial cell‐specific CSE knockout mice (EC‐CSE KO), and investigated vascular function in isolated thoracic aorta, treadmill exercise capacity, and myocardial injury following ischemia‐reperfusion in these mice. Overexpression of CSE in endothelial cells resulted in increased circulating and myocardial H
2
S and NO, augmented endothelial‐dependent vasorelaxation response in thoracic aorta, improved exercise capacity, and reduced myocardial‐reperfusion injury. In contrast, genetic deletion of CSE in endothelial cells led to decreased circulating H
2
S and cardiac NO production, impaired endothelial dependent vasorelaxation response and reduced exercise capacity. However, myocardial‐reperfusion injury was not affected by genetic deletion of endothelial cell CSE.

Conclusions

CSE‐derived H
2
S production in endothelial cells is critical in maintaining endothelial function, exercise capacity, and protecting against myocardial ischemia/reperfusion injury. Our data suggest that the endothelial NO synthase—NO pathway is likely involved in the beneficial effects of overexpression of CSE in the endothelium.
Taxonomic notes on the Alocasia-Colocasia Clade (Araceae) in China I: Alocasia yunqiana, a new species from Tongbiguan Nature Reserve, Yunnan Province

Authors: MA ZHENGXU , LI YIFAN , DAO BAOHUI , YANG WANLIU , LIU BING , YIN JIAN-TAO
Published: September 2020

A new Alocasia species, Alocasia yunqiana, is described and compared with its morphologically related taxa. The novelty is characterized by an oblong-naviculiform-shaped spathe-limb that is strongly hooded and slightly glaucous to glossy during its entire anthesis, a spadix with a sterile interstice and an appendix that are much shorter and thinner than the staminate zone, as well as the dimorphic synandroidia. Detailed information containing description, colored plates and illustration are provided herein.
Goodyera nanshanensis (Orchidaceae, Orchidoideae, Cranichideae, Goodyerinae), a new species from Hunan, China

Authors: WANG XI-LONG , CHEN JUAN , JIN XIAO-HUA
Published: September 2020

Goodyera nanshanensis, a new species from Hunan Province, China, is described and illustrated. Goodyera nanshanensis is morphologically similar to Goodyera recurva, but differs from it by having leaves with irregular transverse white markings, lateral sepals connate about one fifth at base, and lip 2.5 mm long.
The fossil record of the asteroid (Echinodermata) family Chaetasteridae Sladen, 1889 and subfamily Hyalothricinae Fisher, 1911
Authors: GALE ANDREW S.
Published: September 2020

The Cretaceous asteroid Arthraster is referred to the living family Chaetasteridae on the basis of similarities in ossicular arrangement in the abactinal disc and arms. Chaetasterina, previously identified as a chaetasterid, is transferred to the family Asterinidae, subfamily Hyalothricinae, and constitutes the first fossil record of the subfamily.
Annotated checklist and illustrated key to parasitoids (Hymenoptera: Diapriidae, Eulophidae and Pteromalidae) of fruit flies (Diptera, Tephritidae) in Brazil
Authors: SHIMBORI EDUARDO MITIO , COSTA VALMIR ANTONIO , ZUCCHI ROBERTO ANTONIO
Published: September 2020

The hymenopteran parasitoids of pest species of Tephritidae in Brazil are best known by their most prominent species, members of Braconidae and Figitidae. Species in the less-studied families Diapriidae, Eulophidae and Pteromalidae, which are mostly pupal parasitoids, have been largely neglected and the literature on these groups is sparse and scattered. Therefore, their importance as natural enemies of fruit flies is likely underestimated. Here, we present a parasitoid-host-plant checklist of all diapriids, eulophids and pteromalids that parasitize fruit flies of economic importance in Brazil, namely Anastrepha species and Ceratitis capitata. A compilation of information of the seven species of these parasitoids occurring in Brazil—Coptera haywardi Loiácono and Trichopria anastrephae Lima (Diapriidae), Tetrastichus giffardianus Silvestri (Eulophidae), Pachycrepoideus vindemmiae (Rondani), Spalangia endius Walker, S. gemina Bouček and S. simplex Perkins (Pteromalidae)—including their taxonomic status, general biology, and potential as biocontrol agents, is presented. Additionally, we provide an illustrated key to species, aiming to highlight key morphological features and facilitate identification at species level, stimulating future research on these groups.
A Comparison of the U.S. Climate Reference Network Precipitation Data to the Parameter-Elevation Regressions on Independent Slopes Model (PRISM)
Authors: Buban Michael S. , Lee Temple R. , Baker C. Bruce
Published: September 2020

Since drought and excessive rainfall can have significant socioeconomic impacts, it is important to have accurate high-resolution gridded datasets that can help improve analysis and forecasting of these conditions. One such widely used dataset is the Parameter-Elevation Regressions on Independent Slopes Model (PRISM). PRISM uses a digital elevation model (DEM) to obtain gridded elevation analyses and then uses a regression analysis along with approximately 15 000 surface precipitation measurements to produce a 4-km resolution daily precipitation product over the conterminous United States. The U.S. Climate Reference Network (USCRN) consists of 114 stations that take highly accurate meteorological measurements across all regions of the United States. A comparison between the USCRN and PRISM was performed using data from 2006 to 2018. There were good comparisons between the two datasets across nearly all seasons and regions; most mean daily differences were <1 mm, with most absolute daily differences ~5 mm. The most general characteristics were for a net dry bias in the PRISM data in the Southwest and a net moist bias in the southern United States. Verifying the PRISM dataset provides us with confidence it can be used with estimates of evapotranspiration, high-resolution gridded soil properties, and vegetation datasets to produce a daily gridded soil moisture product for operational use in the analyses and prediction of drought and excessive soil moisture conditions.
Impeding fatal violence through third-party diplomacy: The effect of mediation on conflict intensity
Authors: Ruhe Constantin
Published: September 2020

Existing research provides no systematic insights into if and how mediation impedes battle-related deaths. Therefore, this article presents a temporally disaggregated analysis and assesses the effect of mediation on monthly fatal violence. The article predicts that adversaries evaluate opponents’ trustworthiness from both fighting and negotiation behavior. It argues that reducing fighting intensity during negotiations is a sign of cooperation, which can be negotiated by mediators to build trust. Over the course of mediation, the content of negotiations provides information about how genuinely a conflict party is interested in conflict resolution. Only if mediation achieves negotiation of core incompatibilities will conflict parties be willing to reduce fighting intensity. Under these conditions, information revealed in a mediation process can build trust and substantively reduce violence. An empirical analysis of all African conflicts between 1993 and 2007 supports this prediction and shows that on average mediation is followed by substantive and lasting reductions in fatal violence, if mediation discusses the conflict’s main incompatibility. In contrast, mediation on other topics is associated with a small, fleeting reduction in violence. Data of battle-related fatalities in Syria during negotiations as well as qualitative evidence further support the theoretical mechanism and the model prediction. The study concludes that mediation can reduce conflict intensity substantively, if it achieves exchange between conflict parties on the main conflict issues.