bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-bound complement activation products associate with lupus severity in SLE
Authors: Arriens Cristina , Alexander Roberta Vezza , Narain Sonali , Saxena Amit , Collins Christopher E , Wallace Daniel J , Massarotti Elena , Conklin John , Kalunian Kenneth C , Putterman Chaim , Ramsey-Goldman Rosalind , Buyon Jill P , Askanase Anca , Furie Richard A , James Judith A , Bello Ghalib A , Manzi Susan , Ahearn Joseph , O"Malley Tyler , Weinstein Arthur , Dervieux Thierry
Published: May 2020

Objectives

To evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.

Methods

All subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification criteria for SLE. Abnormal CB-CAPs (erythrocyte-bound C4d or B-lymphocyte-bound C4d levels >99th percentile of healthy) and complement proteins C3 and C4 were determined using flow cytometry and turbidimetry, respectively. Lupus severity was estimated using the Lupus Severity Index (LSI). Statistical analysis consisted of multivariable linear regression and groups comparisons.

Results

Abnormal CB-CAPs were more prevalent than low complement values irrespective of LSI levels (62% vs 38%, respectively, p<0.0001). LSI was low (median 5.44, IQR: 4.77–6.93) in patients with no complement abnormality, intermediate in patients with abnormal CB-CAPs (median 6.09, IQR: 5.31–8.20) and high in the group presenting with both abnormal CB-CAPs and low C3 and/or C4 (median 7.85, IQR: 5.51–8.37). Odds of immunosuppressant use was higher in subjects with LSI ≥5.95 compared with subjects with LSI <5.95 (1.60 vs 0.53, p<0.0001 for both). Multivariable regression analysis revealed that higher LSI scores associated with abnormal CB-CAPs—but not low C3/C4—after adjusting for younger age, race and longer disease duration (p=0.0001), which were also independent predictors of disease severity (global R2=0.145).

Conclusion

Abnormalities in complement activation as measured by CB-CAPs are associated with increased LSI.
Detection of unknown atrial fibrillation by prolonged ECG monitoring in an all-comer patient cohort and association with clinical and Holter variables
Authors: Jawad-Ul-Qamar Muhammad , Chua Winnie , Purmah Yanish , Nawaz Mohammad , Varma Chetan , Davis Russell , Maher Abdul , Fabritz Larissa , Kirchhof Paulus
Published: May 2020

Objectives

Prolonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in anunselectedpatient cohort referred from primary care or seen in a teaching hospital.

Methods

We analysed consecutive 7-day ECG recordings in unselected patients referred from different medical specialities and assessed AF detection rates by indication, age and comorbidities.

Results

Seven-day Holter ECGs (median monitoring 127.5 hours, IQR 116 to 152) were recorded in 476 patients (mean age 54.6 (SD 17.0) years, 55.9% female) without previously known AF, requested to evaluate palpitations (n=241), syncope (n=99), stroke or transient ischaemic attack (n=75), dizziness (n=29) or episodic chest pain (n=32). AF was newly detected in 42/476 (8.8%) patients. Oral anticoagulation was initiated in 40/42 (95.2%) patients with newly detected AF. Multivariate logistic regression, adjusted for age, sex and monitoring duration found four clinical parameters to be associated with newly detected AF: hypertension OR=2.54, (1.08 to 8.61) (adjusted OR (95% CI)), p=0.034; previous stroke or TIA OR=4.14 (1.81 to 13.01), p=0.001; left-sided valvular heart disease OR=5.07 (2.48 to 18.70), p<0.001 and palpitations OR=2.86, (1.33 to 10.44), p=0.015.

Conclusions

Open multispeciality access to prolonged ECG monitoring, for example, as part of integrated, cross-sector AF care, can accelerate diagnosis of AF and increase adequate use of oral anticoagulation, especially in older and symptomatic patients with comorbidities.
Anaesthetic complications and management of a great dane presenting with acute respiratory distress
Authors: Ferrero Camilla , Borland Karla
Published: May 2020

Anaesthesia can be challenging in animals with acute respiratory distress. This report details the management of a seven‐year‐old female great dane who initially presented with acute onset tachypnoea and retching. Under general anaesthesia, the dog was initially tachycardic, hypotensive and developed hypoxaemia. CT revealed a hiatal hernia with complete gastric herniation, gastric dilatation and suspected volvulus. At surgery, a type IV hiatal hernia with splenic involvement was confirmed. Following correction of the hernia and repositioning of the stomach and the spleen, oxygen saturation improved, and volume‐controlled ventilation was initiated. The dog recovered from general anaesthesia but developed oliguria, anaemia and became oxygen dependent in the following 48 hours. The dog was subsequently euthanased owing to a grave prognosis.
Growth rates and crown morphology of Abies amabilis in the seedling bank of an ancient subalpine conifer forest
Authors: Antos Joseph A. , McPherson Audrey E. , Guest Heidi J.
Published: May 2020

The population dynamics of shade-tolerant tree species often includes a seedling bank — small trees persisting in the understory until canopy opening allows increased height growth. We studied the growth and morphology of 0.1–1.3 m tall Abies amabilis Douglas ex J. Forbes trees in the seedling bank of an ancient (>1300 years old) subalpine conifer forest on Vancouver Island, western Canada. We determined rates of height growth by counting growth rings at 10 cm intervals along the main stem and assessed crown morphology by measuring the length and location of each branch along the main stem. These small trees were very old (mean basal ring count, 112 years) and grew very slowly, taking on average 170 years to reach a height of 1 m. Instead of the typical conical form of open-grown Abies Mill., seedling bank individuals had flat crowns. Most branches were near the top of the main stem. The maximum distance along the main stem plus a branch was 1.6 times the main stem length, indicating that resource allocation is focused on lateral growth. The ability to grow slowly and adjust crown morphology allows seedling bank trees to persist for decades to centuries and to retain the possibility of release and growth into the canopy.
Pure States of Maximum Uncertainty with Respect to a Given POVM
Authors: Szymusiak Anna
Published: May 2020

One of the differences between classical and quantum world is that in the former we can always perform a measurement that gives certain outcomes for all pure states, while such a situation is not possible in the latter one. The degree of randomness of the distribution of the measurement outcomes can be quantified by the Shannon entropy. While it is well known that this entropy, as a function of quantum states, needs to be minimized by some pure states, we would like to address the question how ‘badly’ can we end by choosing initially any pure state, i.e., which pure states produce the maximal amount of uncertainty under given measurement. We find these maximizers for all highly symmetric POVMs in dimension 2, and for all SIC-POVMs in any dimension.
The Econometrics of Static Games
Authors: Aradillas-López Andrés
Published: May 2020

This article reviews the econometrics of static games, with a focus on discrete-choice cases. These models have been used to study a rich variety of empirical problems, ranging from labor force participation to entry decisions. We outline the components of a general game and describe the problem of doing robust inference in the presence of multiple solutions, as well as the different econometric approaches that have been applied to tackle this problem. We then describe the specific challenges that arise in different variations of these models depending on whether players are assumed to have complete or incomplete information, as well as whether or not nonequilibrium play is allowed. We describe the results in 2 × 2 games (the most widely studied games in econometrics), and we present extensions and recent results in games with richer action spaces. Areas for future research are also discussed.
Dynamic Taxation
Authors: Stantcheva Stefanie
Published: May 2020

This article reviews recent advances in the study of dynamic taxation, considering three main approaches: the dynamic Mirrlees, the parametric Ramsey, and the sufficient statistics approaches. In the first approach, agents’ heterogeneous abilities to earn income are private information and evolve stochastically over time. Dynamic taxes are not restricted ex ante and are set for redistribution and insurance considerations. Capital is taxed only in order to improve incentives to work. Human capital is optimally subsidized if it reduces posttax inequality and risk on balance. The Ramsey approach specifies ex ante restricted tax instruments and adopts quantitative methods, which allow it to consider more complex and realistic economies. Capital taxes are optimal when age-dependent labor income taxes are not possible. The newer and tractable sufficient statistics approach derives robust tax formulas that depend on estimable elasticities and features of the income distributions. It simplifies the transitional dynamics thanks to a newly defined criterion, the utility-based steady-state approach, which prevents the government from exploiting sluggish responses in the short run. Capital taxes are here based on the standard equity-efficiency trade-off.
Risk Factors Associated with Fatal Dengue Hemorrhagic Fever in Adults: A Case Control Study
Authors: Medagama Arjuna , Dalugama Chamara , Meiyalakan Gukes , Lakmali Darshani
Published: May 2020

Background. Dengue is endemic in most parts of the tropics with a significant mortality of 1–5%. Although individual case reports and case series have been published, large-scale case controls studies are few. The objective of this study was to find clinical and laboratory predictors of mortality in dengue. Methods. Hospital case record based case control study was performed. Results. Twenty fatalities with 80 controls were analyzed. Clinical parameters of postural dizziness (OR 3.2; 95% CI 1.1–8.9), bleeding (OR 31.9; 95% CI 6.08–167.34), presence of plasma leakage (OR 64.6; 95% CI 7.45–560.5), abdominal tenderness (OR 2.24; 95% CI 0.79–6.38), and signs of cardiorespiratory instability at admission increased the risk of dying from dengue. Altered consciousness was exclusively seen in 20% of cases. Laboratory parameters of elevated CRP (OR 1.652; 95% CI 1.28–2.14), AST, or ALT > 500 IU/L (OR 52.5; 95% CI 12.52–220.1) and acute kidney injury (AKI) (OR 103.5; 95% CI 13.26–807.78) during hospital stay increased the odds of dying. Need for assisted ventilation and multiorgan dysfunction (MOD) were exclusively seen in the cases. Multivariate logistic regression revealed bleeding at admission, AKI, and elevated hepatic transaminase >500 IU/L to be independent predictors of mortality. Conclusions. This case control study revealed that mortality from dengue could be predicted using clinical parameters at admission and low cost routine laboratory investigations.
Chondro-Osseous Metaplasia in Ependymoma: A Rare Histopathological Finding
Authors: Alkhaibary Ali , AlSufiani Fahd , Alassiri Ali H. , Almuntashri Makki , Al Qutub Salma Tarik
Published: May 2020

Ependymoma is a circumscribed glioma composed of uniform glial cells with bland nuclei in a fibrillary matrix. It is characterized by the presence of perivascular pseudorosettes. Unusual histopathological findings have rarely been reported in ependymomas, 0.5% of all diagnosed cases. Such unusual and exceedingly rare histological findings include osseous or chondroid metaplasia. To the best of our knowledge, only 15 cases of osseocartilaginous ependymomas have been reported in English literature. We report a 3-year-old boy who presented with ataxia, vomiting, and headache for three months. Radiological imaging revealed a posterior fossa lesion. Histopathological examination of the lesion confirmed a posterior fossa ependymoma with chondro-osseous metaplasia. The present case outlines the clinical presentation, histopathological findings, and outcome of chondro-osseous metaplasia in ependymomas. To date, the etiology of chondro-osseous metaplasia in ependymomas remains uncertain. Further research exploring such phenomenon is of paramount importance to explain how these tumors develop.
Reversible Fragile Watermarking Scheme for Relational Database Based on Prediction-Error Expansion
Authors: Hamadou Ali , Camara Lanciné , Issaka Hassane Abdoul Aziz , Naroua Harouna
Published: May 2020

The protection of database systems content using digital watermarking is nowadays an emerging research direction in information security. In the literature, many solutions have been proposed either for copyright protection and ownership proofing or integrity checking and tamper localization. Nevertheless, most of them are distortion embedding based as they introduce permanent errors into the cover data during the encoding process, which inevitably affect data quality and usability. Since such distortions are not tolerated in many applications, including banking, medical, and military data, reversible watermarking, primarily designed for multimedia content, has been extended to relational databases. In this article, we propose a novel prediction-error expansion based on reversible watermarking strategy, which not only detects and localizes malicious modifications but also recovers back the original data at watermark detection. The effectiveness of the proposed method is proved through rigorous theoretical analysis and detailed experiments.
Deep Convolutional Neural Networks-Based Automatic Breast Segmentation and Mass Detection in DCE-MRI
Authors: Jiao Han , Jiang Xinhua , Pang Zhiyong , Lin Xiaofeng , Huang Yihua , Li Li
Published: May 2020

Breast segmentation and mass detection in medical images are important for diagnosis and treatment follow-up. Automation of these challenging tasks can assist radiologists by reducing the high manual workload of breast cancer analysis. In this paper, deep convolutional neural networks (DCNN) were employed for breast segmentation and mass detection in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). First, the region of the breasts was segmented from the remaining body parts by building a fully convolutional neural network based on U-Net++. Using the method of deep learning to extract the target area can help to reduce the interference external to the breast. Second, a faster region with convolutional neural network (Faster RCNN) was used for mass detection on segmented breast images. The dataset of DCE-MRI used in this study was obtained from 75 patients, and a 5-fold cross validation method was adopted. The statistical analysis of breast region segmentation was carried out by computing the Dice similarity coefficient (DSC), Jaccard coefficient, and segmentation sensitivity. For validation of breast mass detection, the sensitivity with the number of false positives per case was computed and analyzed. The Dice and Jaccard coefficients and the segmentation sensitivity value for breast region segmentation were 0.951, 0.908, and 0.948, respectively, which were better than those of the original U-Net algorithm, and the average sensitivity for mass detection achieved 0.874 with 3.4 false positives per case.
[Retracted] Efficacy of Neoadjuvant Chemotherapy with Epirubicin and Cyclophosphamide and Weekly Paclitaxel and Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Carcinoma: A Real‐World Study
Authors: Zhang Mengmeng , Li Ling , Zhang Shiyong , Zhu Wenlong , Yang Senguo , Di Guangsheng , Ma Xiaoxia , Yang Haisong
Published: May 2020

Background. Trastuzumab has been introduced a decade ago and demonstrated improvement in the prognosis in patients with human epidermal growth factor receptor 2‐ (HER2‐) positive (+) breast carcinoma (BC). This study is aimed at evaluating the efficacy of epirubicin/cyclophosphamide with weekly paclitaxel‐trastuzumab as neoadjuvant chemotherapies in HER2+ BC patients. Methods. A total of 234 HER2+ BC patients were given neoadjuvant chemotherapy (NAC) between 2010 and 2016. The primary endpoints were pathologic complete response (pCR) and disease‐free survival (DFS). Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were conducted. Results. The pCR (30.4% vs. 14.8%; P = 0.004) and DFS (P = 0.036) showed significant differences between patients administered with neoadjuvant trastuzumab therapy and those who did not. Multivariate logistic regression analysis showed that neoadjuvant trastuzumab treatment was regarded as an independent predictor of pCR. Patients with pCR had prolonged DFS (P = 0.025). In patients who did not achieve pCR (non‐pCR), those who received trastuzumab had more prolonged DFS (P = 0.046). The luminal B/HER2+ subtypes had prolonged DFS when compared with nonluminal B/HER2+ subtypes (P = 0.010). The luminal B/HER2+ subgroup also showed improved DFS in non‐pCR patients (P = 0.010). In the subgroup of non‐pCR, the luminal B/HER2+ subgroup administered with trastuzumab showed no superior DFS (P = 0.168). However, a positive result was observed in patients without trastuzumab (P = 0.039). Multivariate analysis showed cT stage (P = 0.006) and tumor grade (P = 0.041), considering them as significant prognostic factors of DFS. Conclusions. HER2+ BC patients showed improvement in pCR and DFS after neoadjuvant trastuzumab treatment. Patients without pCR had prolonged DFS after trastuzumab maintenance. Although the prognosis of luminal B/HER2+ BC showed favorable outcomes in the non‐pCR subgroup, those receiving trastuzumab showed no survival advantage.
Two-Parameter Regularization Method for a Nonlinear Backward Heat Problem with a Conformable Derivative
Authors: Ho Vu , O’Regan Donal , Van Hoa Ngo
Published: May 2020

In this paper, we consider the nonlinear inverse-time heat problem with a conformable derivative concerning the time variable. This problem is severely ill posed. A new method on the modified integral equation based on two regularization parameters is proposed to regularize this problem. Numerical results are presented to illustrate the efficiency of the proposed method.
Autophagy Suppresses Toll‐Like Receptor 3‐Mediated Inflammatory Reaction in Human Epidermal Keratinocytes
Authors: Li Xue Mei , Jung Kyung Eun , Yim Su Hyuk , Hong Dong Kyun , Kim Chang Deok , Hong Jeong Yeon , Lee Ho Jung , Lee Sung Yul , Kim Jung Eun , Park Chang Wook
Published: May 2020

Autophagy, one mechanism of programmed cell death, is fundamental to cellular homeostasis. Previous studies have identified autophagy as a novel mechanism by which cytokines control the immune response. However, its precise role in immune‐related inflammatory skin diseases such as psoriasis remains unclear. Thus, this study explored the functional role of autophagy in psoriatic inflammation of epidermal keratinocytes. Strong light chain 3 immunoreactivity was observed in epidermal keratinocytes of both human psoriatic lesions and imiquimod‐induced mice psoriatic model, and it was readily induced by polycytidylic acid (poly (I:C)), which stimulates Toll‐like receptor 3 (TLR3), in human epidermal keratinocytes in vitro. Rapamycin‐induced activation of autophagy significantly reduced poly (I:C)‐induced inflammatory reaction, whereas, inhibition of autophagy by 3‐methyladeine increased that. Our results indicate that the induction of autophagy may attenuate TLR3‐mediated immune responses in human epidermal keratinocytes, thus providing novel insights into the mechanisms underlying the development of inflammatory skin diseases including psoriasis.
Histopathology of Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka
Authors: Wijesinghe Harshima , Gunathilaka Nayana , Semege Saveen , Pathirana Nishantha , Manamperi Nuwani , de Silva Chandu , Fernando Deepika
Published: May 2020

Cutaneous leishmaniasis (CL) is a neglected tropical disease that is gaining importance in Sri Lanka and internationally. The clinical presentation, pathology, and method of parasite elimination in CL vary according to the species. Leishmania donovani is the causative organism for leishmaniasis in Sri Lanka. This collaborative cross‐sectional study describes the clinicopathological features of cutaneous leishmaniasis among personnel of the tri‐forces serving in the North and East of the country. The histology of fifty cases of CL confirmed by at least two methods (slit skin smear, lesion aspirate, tissue impression, and histology) was reviewed. The parasitic load was assessed semiquantitatively. The histological features were correlated with the clinical presentation and organism load. The majority (89.8%; n = 44) presented with a single lesion mostly located in the upper limb (69.4%). The lesion types included papule (34.7%), nodule (32.7%), and an ulcer (30.6%). The evolution time of lesions averaged 31.55 weeks. Epidermal changes were observed in 49 of the biopsies and included hyperkeratosis (90.0%; n = 45), acanthosis (44.0%; n = 22), atrophy (34.0%; n = 17), and interface change (66%; n = 33). Dermal changes were seen in all cases and were characterized by a lymphohistioplasmacytic inflammatory infiltrate of variable intensity with ill‐formed granuloma in 19 cases (38%) and well‐formed epithelioid granulomas in 22 cases (44%). Focal necrosis was present in 20% (n = 10). Leishmania amastigote forms were observed in 88% (n = 44). Transepidermal elimination (P = 0.025), granuloma (P = 0.027) formation, and type of lesion (P = 0.034) were significantly associated with the organism load. Granuloma formation was associated with a reduction in organism load, indicating that the macrophage activation played an important role in the control of the organism.
Results of Positive Solutions for the Fractional Differential System on an Infinite Interval
Authors: Wang Ying , Yang Jun , Zi Yumei
Published: May 2020

The chief topic of this paper is to investigate the fractional differential system on an infinite interval. By introducing an appropriate compactness criterion in a special function space and applying the Schauder fixed-point theorem and the Banach contraction mapping principle, we established the results for the existence and uniqueness of positive solutions. An example is then given to show the utilization of the main results.
Optimizing the Cargo Location Assignment of Retail E-Commerce Based on an Artificial Fish Swarm Algorithm
Authors: Zhang Shuiwang , Fu Linping , Chen Rong , Mei Yu
Published: May 2020

An efficient storage strategy for retail e-commerce warehousing is important for minimizing the order retrieval time to improve the warehouse-output efficiency. In this paper, we consider a model and algorithm to solve the cargo location problem in a retail e-commerce warehouse. The problem is abstracted into storing cargo on three-dimensional shelves, and the mathematical model is built considering three objectives: efficiency, stability, and classification. An artificial swarm algorithm is designed to solve the proposed models. Computational experiments performed on a warehouse show that the proposed approach is effective at solving the cargo location assignment problem and is significant for the operation and organization of a retail e-commerce warehouse.
Association of IL-1β, IL-6, TNF-α, and TGFβ1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome
Authors: Alkhuriji Afrah F. , Al Omar Suliman Y. , Babay Zainb A. , El-khadragy Manal F. , Mansour Lamjed A. , Alharbi Wazirah G. , Khalil Mahmoud I.
Published: May 2020

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated complication of polycystic ovary syndrome (PCOS) which is an endocrine malfunction disease. Patients with PCOS may have several underlying contributing and interrelated factors, which have been reported in women with RSA. The incidence rate between PCOS and RSA remains uncertain. The aim of this study is to determine the possible association of IL-1β-511C/T, IL-6-174G/C, TNF-α-1031T/C, and TGFβ1-509T/C with RSA patients with or without PCOS. A total of 140 RSA patients, 70 of which were PCOS patients, and 140 healthy females with no history of RSA or PCOS were included in this study. PCR amplification, genotyping, and sequence analysis were employed to investigate the presence of the polymorphisms. The genotypic and allelic frequencies were calculated separately for each subject. Out of the four studied polymorphisms, the IL-1β-511C/T genotype in RSA without PCOS patients (12.7%) was significantly different compared with that in control subjects (p=0.047). For IL-6-174C/G, there was a tendency towards more CC carriers among RSA with PCOS patients (10%) than in controls (3%). The GG genotype in RSA women with PCOS (60%) was significantly different compared with that in control subjects (p=0.033), and the GC genotype in RSA with PCOS patients (30%) showed a marginal significant difference compared with that in control subjects (p=0.050). Significant difference was identified in the allelic frequencies in RSA patients with PCOS compared to controls (p=0.025). IL-6-174G/C and TNF-α-1031T/C polymorphisms are significantly associated with RSA patients in Saudi patients with PCOS, while the IL-1β-511C/T polymorphism is significantly associated with RSA patients without PCOS.
An Approach for Stability Analysis of Gas/Fluid-Filled Cylindrical Hole in Laminated Materials
Authors: Leng Song , Hou Li , Duan Yang
Published: May 2020

An explicit analytical workflow for cylindrical hole stability analyses in general laminated materials that possess transversely isotropic (TI) anisotropy is presented. In this approach, the calculation of the distribution of the stresses around a cylindrical hole and the failure evaluation at the hole wall consider the effects of both material elasticity anisotropy and strength anisotropy caused by material laminated structures. Material strength anisotropy is assumed to be caused by the sliding of preexisting weakness planes oriented parallel to the isotropic plane of the material. The effect of anisotropy on strength is modeled by combining a shear failure criterion for the intact matrix and a weak plane failure criterion for the planes of weakness. We derive critical pressure solutions for the stability of the intact matrix around a hole filled with gas or fluid based on the Mohr–Coulomb failure criterion and Drucker–Prager failure criterion; either one of them can be combined with the weak plane failure criterion to give the solution for hole wall shear failure pressure. The solution for hole wall fracture initiation pressure is derived based on the tensile failure criterion. This approach can be applied to holes of arbitrary orientation in general laminated materials.
Management of Lateral Epicondylitis: A Narrative Literature Review
Authors: Ma Kun-Long , Wang Hai-Qiang
Published: May 2020

Lateral epicondylitis, also termed as “tennis elbow,” is the most common cause of elbow pain and dysfunction, mainly resulting from repetitive gripping or wrist extension during various activities. The exact pathogenesis remains largely elusive with putative tendinosis, a symptomatic degenerative process of the local tendon. It is usually diagnosed by clinical examinations. Sometimes, additional imaging is required for a specific differential diagnosis. Although most cases can be self-healing, the optimal treatment strategy for chronic lateral epicondylitis remains controversial. This article presents a landscape of emerging evidence on lateral epicondylitis and focuses on the pathogenesis, diagnosis, and management, shedding light on the understandings and treatment for healthcare professionals.
Assessment of Levels of Natural Radioactivity in Sand Samples Collected from Ekalakala in Machakos County, Kenya
Authors: Munyao Lucia Nyiva , Ketui Daniel Kipngetich , Otieno Calford , Chege Margaret Wairimu
Published: May 2020

Construction sand is naturally polluted with radionuclides of terrestrial origin. In this study, specific activities of 238U, 232Th, and 40K in 30 sand samples collected along the Ekalakala River, Machakos County, Kenya, were measured using a high-purity germanium γ-ray spectrometer. The specific activities ranged between 9.7 Bqkg−1 and 24.0 Bqkg−1, 11.5 Bqkg−1 and 26.2 Bqkg−1, and 820 Bqkg−1 and 1850 Bqkg−1 for 238U, 232Th, and 40K, respectively. While the mean specific activities for 238U and 232Th were less than half of the world average values of 33 Bqkg−1 and 45 Bqkg−1, respectively, the average specific activity of 40K was significant since it was three times the global mean value of 420 Bqkg−1. A calculated absorbed radiation dose rate for the sand varied between 46.8 nGyh−1 and 94.2 nGyh−1 with a mean of 68.5 ± 13.3 nGyh−1. This is not significantly different from the world average dose rate of 60 nGyh−1 for geological samples. The AEDR and Hex had maximum values of 0.29 mSvy−1 and 0.52, respectively, both within the recommended limits of radiation exposure for members of the general public. Based on these results, the sand from Ekalakala River does not pose significant health implication to the sand harvesters as well as the inhabitants of the houses constructed using this sand.
The Mechanism of Zinc Sulfate in Improving Fertility in Obese Rats Analyzed by Sperm Proteomic Analysis
Authors: Ma Jing , Han Ruiyu , Li Yuanlong , Cui Tong , Wang Shusong
Published: May 2020

This study investigates the mechanism underlying the improving effect of zinc on fertility in obese rats using proteomics. The effects of three different doses of ZnSO4 on spermatogenesis and hormone levels were studied. Testicular spermatogenesis was observed by HE staining. Serum estrogen and testosterone levels were measured by chemiluminescent microparticle immunoassay. Sperm proteomic analysis was performed by liquid chromatography‐mass spectrometry. The DAVID database was used to perform the GO enrichment analysis and KEGG pathway analysis of the differentially expressed genes, and the STRING online database was used to construct a PPI network. The sperm count, sperm motility, and testosterone hormones of the ZnSO4‐treated rats group were increased. ZnSO4 improved testicular structure and spermatogenesis abnormalities caused by obesity. Proteomic analysis showed that there were 401 differentially expressed proteins in a total of 6 sperm samples from the ZnSO4‐treated group and the obesity groups. Differential proteins were input into the DAVID website. The 341 identified proteins were then classified according to their biological functions. The KEGG analysis showed that the enriched signal pathways included glycolysis/gluconeogenesis, carbon metabolism, citrate cycle, fatty acid metabolism, and pyruvate metabolism. Some proteins were shown to be associated with valine, leucine, and isoleucine degradation pathways. STRING analysis obtained 36 node proteins. Cytoscape analysis showed that these proteins mainly participated in nine networks including metabolic process, oxidation‐reduction, aerobic respiration, RNA splicing, and glutathione conjugation. ZnSO4 may improve the fertility of obese male rats by regulating protein expression related to metabolism, inflammation, and sperm maturation.
Rac Signaling Drives Clear Cell Renal Carcinoma Tumor Growth by Priming the Tumor Microenvironment for an Angiogenic Switch
Authors: Goka Erik T. , Chaturvedi Pallavi , Lopez Dayrelis T. Mesa , Lippman Marc E.
Published: May 2020

Clear cell renal cell carcinoma (ccRCC) remains a common cause of cancer mortality. Better understanding of ccRCC molecular drivers resulted in the development of antiangiogenic therapies that block the blood vessels that supply tumors with nutrients for growth and metastasis. Unfortunately, most ccRCC patients eventually become resistant to initial treatments, creating a need for alternative treatment options. We investigated the role of the small GTPase Rac1 in ccRCC. Analysis of ccRCC clinical samples indicates that Rac signaling drives disease progression and predicts patients with poorer outcomes. Investigation of Rac1 identifies multiple roles for Rac1 in the pathogenesis of ccRCC. Rac1 is overexpressed in RCC cell lines and drives proliferation and migratory/metastatic potential. Rac1 is also critical for endothelial cells to grow and form endothelial tubular networks potentiated by angiogenic factors. Importantly, Rac1 controls paracrine signaling of angiogenic factors including VEGF from renal carcinoma cells to surrounding blood vessels. A novel Rac1 inhibitor impaired the growth and migratory potential of both renal carcinoma cells and endothelial cells and reduced VEGF production by RCC cells, thereby limiting paracrine signaling both in vitro and in vivo. Lastly, Rac1 was shown to be downstream of VEGF receptor (VEGFR) signaling and required for activation of MAPK signaling. In combination with VEGFR2 inhibitors, Rac inhibition provides enhanced suppression of angiogenesis. Therefore, targeting Rac in ccRCC has the potential to block the growth of tumor cells, endothelial cell recruitment, and paracrine signaling from tumor cells to other cells in the tumor microenvironment.
Emerging Pharmacological Treatment in Nonalcoholic Steatohepatitis
Authors: Schattenberg Jörn M.
Published: May 2020

Background: The increasing prevalence of nonalcoholic ­fatty liver disease has led to a strong demand for an optimal therapeutic approach. At present, guidelines recommend lifestyle changes, but it has become apparent that pharmacotherapy will be required in patients with advanced disease to prevent the progression to end-stage liver disease and potentially improve extrahepatic outcomes. Summary: This review discusses current pharmacological approaches focusing on substances studied in pivotal trials and selected phase 2 trials in patients with nonalcoholic steatohepatitis (NASH) and fibrosis. Key Message: Currently, several compounds are subjected to clinical testing to explore predominantly anti-inflammatory, anti-fibrotic, and metabolic treatment for NASH. With current response rates around 20%, the combination of several drugs targeting more than one pathway could lead to increased treatment success in the future.
Relationship between Thyroid and Kidney Function: Analysis from the Korea National Health and Nutrition Examination Survey Between 2013 and 2015
Authors: Kim Sang Hyuk , Min Hyang Ki , Lee Sung Woo
Published: May 2020

Introduction: Thyroid function is evaluated by thyroid stimulating hormone (TSH) and free thyroxine (fT4). Although many studies have indicated an intimate relationship between thyroid hormones and kidney functions, reports about the simultaneous evaluation of TSH and fT4 are rare. Objective: We aimed to analyze the association between TSH and kidney function, with emphasis on a potential nonlinear relationship, and identify an independent relationship between fT4 and kidney function. Methods: We reviewed the data of 7,061 subjects in the Korea National Health and Nutrition Examination Surveys who were randomly subsampled for thyroid function evaluation between 2013 and 2015. A total of 5,578 subjects were included in the final analysis, after excluding people <18 years old, and those with a short fasting time, abnormal fT4 levels, and thyroid disease or related medications. Creatinine-based estimated glomerular filtration rate (eGFR) was used to define kidney function. Results: A 1 mmol/L increase of logarithmic TSH was associated with decreased eGFR (β: –1.8; 95% CI –2.3 to –1.2; p < 0.001), according to multivariate linear regression analysis. On the multivariate generalized additive model plot, TSH demonstrated an L-shaped relationship with eGFR, showing a steeper slope for 0–4 mIU/L of TSH. A 1 µg/dL increase of fT4 was also associated with decreased eGFR (β: –7.0; 95% CI –0.94 to –4.7; p < 0.001) on the multivariate linear regression analysis; this association was reversed after adjusting for age. On the mediation analysis, the indirect effect via age and direct effect per 1 µg/dL increase of fT4 on eGFR was 9.9 (8.1 to 11.7, p < 0.001) and –7.1 (–9.3 to –4.8, p < 0.001), respectively. Conclusions: Increased TSH was associated with decreased eGFR, particularly in the reference range. The direct effect of increased fT4 was decreased eGFR, which may be affected indirectly by age.
Impact of Anal Fissure on Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness: A Case-Control Study
Authors: Luri-Prieto Paloma , Candela-Gomis Asunción , Palazón-Bru Antonio , Navarro-Cremades Felipe , Gil-Guillén Vicente Francisco , Compañ-Rosique Antonio Fernando
Published: May 2020

Introduction: Scientific literature on determining patterns of personality traits in patients with anal fissure is limited. Objectives: To determine whether certain common psychological traits are associated with anal fissure. Methods: A case-control study was carried out in Spain in 2016–2017. Patients with acute or chronic idiopathic anal fissure (n = 35) and controls (n = 32) were recruited. The main outcome measures were those defined in the NEO-FFI questionnaire, validated in Spain, which was administered to all the participants. This questionnaire evaluates the following traits: neuroticism, extraversion, openness, agreeableness, and conscientiousness. Results: Three significant traits were noted: (1) greater neuroticism in the cases (OR 1.19, 95% CI 1.08–1.32, p < 0.001, AUC 0.77), (2) greater openness to experience in the controls (OR 0.90, 95% CI 0.83–0.98, p = 0.015, AUC 0.69), and (3) greater conscientiousness in the controls (OR 0.91, 95% CI 0.83–1.00, p = 0.049, AUC 0.69). Conclusions: The cases mainly presented higher levels of neuroticism and lower levels of openness to experience and conscientiousness. Further studies are needed to corroborate our results.
Hyaluronsäure- als Alternative zu Eigenserum-Augentropfen: Erste klinische Ergebnisse zu Augentropfen mit langkettiger Hyaluronsäure
Authors: Beck Ria , Stachs Oliver , Koschmieder Anita , Mueller-Lierheim Wolfgang G.K. , Peschel Sabine , van Setten Gysbert-Botho
Published: May 2020

Einleitung: Eigenserum-Augentropfen (ESAT) werden zur Behandlung des Trockenen Auges in besonders schweren Fällen eingesetzt. Nachdem mit ihrer Anwendung einmal begonnen wurde, gilt eine Rückkehr zu anderen gleitfördernden Augentropfen oder sonstigen Therapieoptionen auf dem Markt als unmöglich. Material und Methoden: In einer randomisierten Studie wurde 11 Patienten, die seit mindestens 3 Monaten mit ESAT behandelt wurden, angeboten, stattdessen Augentropfen mit langkettiger Hyaluronsäure zu verwenden. Die Kontrollgruppe (n = 5) setzte ihre Behandlung mit ESAT fort. Die Verumgruppe (n = 6) wendete Augentropfen mit sehr langkettiger Hyaluronsäure (Comfort Shield®) anstelle der ESAT an. Ergebnisse: Von 4 der anfänglich 6 Patienten in der Verumgruppe, die die Studie abschlossen, entschieden sich 2 (50%) dafür, auch über den Untersuchungszeitraum hinaus bei den Augentropfen mit langkettiger Hyaluronsäure zu bleiben, die anderen beiden kehrten zu ihrer vorherigen Therapie mit ESAT zurück. Die Kontrollgruppe führte ihre Behandlung fort wie zuvor und schloss die Studie nach 8 Wochen ab. Schlussfolgerung: Erstmals erwiesen sich künstliche Augentropfen in Form von langkettigen Hyaluronsäure-Augentropfen als akzeptable Alternative zu ESAT. Einige Patienten empfanden diese Tropfen als noch besser als die Tropfen aus ihrem Eigenserum. Dies ist die erste Evidenz, dass durch Optimierung der Struktur des Hyaluronsäuremoleküls Augentropfen hergestellt werden könnten, die im Vergleich zu anderen Tränenersatzmitteln und sogar zu Eigenserum als besser wahrgenommen werden. Dies eröffnet neue Perspektiven für die Behandlung von Patienten mit schweren Fällen des Trockenen Auges.
Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma
Authors: Desai Vishal , Patel Kevin , Sheth Ravi , Barlass Usman , Chan Yuet-Ming , Sclamberg Joy , Bishehsari Faraz
Published: May 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate, partly due to delayed diagnosis. Identifying high-risk individuals could lead to early detection and improve survival. A number of risk factors such as alcohol consumption and metabolic syndrome are associated with fatty infiltration of the pancreas. Experimental models show that a fatty pancreas promotes tissue inflammation and fibrosis, which could promote PDAC. Methods: We conducted a case-control study in a single-university tertiary hospital. Sixty-eight PDAC cases with recent non-contrast computed tomography (CT) and 235 controls were studied. The controls had no history of malignancy and underwent CT colonography for cancer screening in the same period. Pancreatic fat was estimated by calculating pancreatic (P) attenuation, corrected to splenic (S) attenuation, measured in three 1.0-cm2 regions of the pancreas. The P.S100 value calculated was used to estimate fatty infiltration of the pancreas (FIP), with a lower P.S100 representing a higher FIP. Results: The PDAC patients had a lower BMI and a higher rate of type 2 diabetes mellitus. The P.S100 was lower in cases than in controls (86.452 vs. 92.414, p = 4.016e-06), suggesting that FIP is higher with PDAC. The risk of developing PDAC steadily increased significantly for the quartiles with a higher FIP compared to the low FIP quartile. No correlation between BMI and FIP (r = –0.1031179; 95% confidence interval [CI] –0.22267106 to 0.01949092) was found. Adjusting for confounders (age, sex, BMI, and DM), the risk of developing PDAC according to the FIP was estimated to be 3.75 (95% CI 1.9234408–7.993337; p = 0.000171). FIP was stable before and after the diagnosis of PDAC in 9 cases with prior CT scans when no pancreatic tumor was identifiable. Conclusion: Fatty pancreas is associated with an increased risk of pancreatic cancer. Once confirmed in larger-scale studies, these findings could help to identify at-risk individuals, particularly in high-risk groups such as chronic alcohol consumers
Nonmosaic Trisomy 19p13.3p13.2 Resulting from a Rare Unbalanced t(Y;19)(q12;p13.2) Translocation in a Patient with Pachygyria and Polymicrogyria
Authors: Martínez Anaya Daniel , Fernández Hernández Liliana , González del Angel Ariadna , Alcántara Ortigoza Miguel A. , Ulloa Avilés Verónica , Pérez Vera Patricia
Published: May 2020

Nonmosaic trisomy involving 19p13.3p13.2 is a very uncommon abnormality. At present, only 12 cases with this genetic condition have been reported in the literature. However, the size of the trisomic fragment is heterogeneous and thus, the clinical spectrum is variable. Herein, we report the clinical and cytogenetic characterization of a 5-year-old boy with nonmosaic trisomy 19p13.3p13.2 (7.38 Mb), generated by a derivative Y chromosome resulting from a de novo unbalanced translocation t(Y;19)(q12;p13.2). We demonstrated the integrity of the euchromatic regions in the abnormal Y chromosome to confirm the pure trisomy 19p. Our patient shares some clinical features described in other reported patients with pure trisomy 19p, such as craniofacial anomalies, developmental delay, and heart defects. Different to previous reports, our case exhibits frontal pachygyria and polymicrogyria. These additional features contribute to further delineate the clinical spectrum of trisomy 19p13.3p13.2.
NSCLC im Stadium II: Strahlentherapie und Einsatz von Chemotherapie bei nicht operablen Patienten
Authors: Möller Miriam , Schütte Wolfgang
Published: May 2020

Objectives: Curative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome. Materials and methods: A retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention. Results: A total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes. Conclusions: Among patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.
Outcome of Extracorporeal Photopheresis as an Add-On Therapy for Antibody-Mediated Rejection in Lung Transplant Recipients
Authors: Benazzo Alberto , Worel Nina , Schwarz Stefan , Just Ulrike , Nechay Anna , Lambers Christoph , Böhmig Georg , Fischer Gottfried , Koren Daniela , Muraközy Gabriela , Knobler Robert , Klepetko Walter , Hoetzenecker Konrad , Jaksch Peter
Published: May 2020

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.