bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Insights into Alzheimer's Disease
Authors: Latimer Caitlin S. , Lucot Katherine L. , Keene C. Dirk , Cholerton Brenna , Montine Thomas J.
Published: January 2021

Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires autopsy examination of the brain to identify amyloid plaques and neurofibrillary degeneration. Over the past 100 years, there has been remarkable progress in our understanding of the underlying pathophysiologic processes, pathologic changes, and clinical phenotypes of AD, largely because genetic pathways that include but expand beyond amyloid processing have been uncovered. This review discusses the current state of understanding of the genetics of AD with a focus on how these advances are both shaping our understanding of the disease and informing novel avenues and approaches for development of potential therapeutic targets.
The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity
Authors: Kumar Vinay
Published: January 2021

I have had the singular opportunity to perform research and to participate in medical education. Not unexpectedly, people have asked me which of the two was more important to me. My answer has always been and remains that I am equally passionate about research and teaching. My research has been curiosity driven and not purposeful; hence, I was willing to take risks. That my research led to the discovery of natural killer cells and the unraveling of the molecular basis of a human disease was an unexpected reward. By contrast, my interest in medical education was purposeful, with the goal of improving healthcare by teaching pathology as the scientific foundation of medicine. It started with participation in Robbins pathology texts but progressed toward development of technology-based tools for medical education. This was driven by the belief that technology, by providing equal access to knowledge across the world, can be a powerful democratizing force.
Climate Change, Food Supply, and Dietary Guidelines
Authors: Binns Colin W. , Lee Mi Kyung , Maycock Bruce , Torheim Liv Elin , Nanishi Keiko , Duong Doan Thi Thuy
Published: January 2021

Food production is affected by climate change, and, in turn, food production is responsible for 20–30% of greenhouse gases. The food system must increase output as the population increases and must meet nutrition and health needs while simultaneously assisting in achieving the Sustainable Development Goals. Good nutrition is important for combatting infection, reducing child mortality, and controlling obesity and chronic disease throughout the life course. Dietary guidelines provide advice for a healthy diet, and the main principles are now well established and compatible with sustainable development. Climate change will have a significant effect on food supply; however, with political commitment and substantial investment, projected improvements will be sufficient to provide food for the healthy diets needed to achieve the Sustainable Development Goals. Some changes will need to be made to food production, nutrient content will need monitoring, and more equitable distribution is required to meet the dietary guidelines. Increased breastfeeding rates will improve infant and adult health while helping to reduce greenhouse gases.
Electrolyte Dependency on Ca2+ Insertion and Extraction Properties of V2O5
Authors: Murata Yoshiaki , Inada Ryoji , Sakurai Yoji
Published: January 2021

The influence of the electrolyte structure on the Ca2+ ion insertion and extraction properties of V2O5 was studied by changing the electrolyte concentration or solvent. The electrolyte structure was analyzed by Raman spectroscopy. The most significant changes were found in the molar ratio of the contact ion pair (CIP) in the total ionic species. Among the various electrolytes, 0.3 M Ca(TFSI)2 dissolved in ethylene carbonate and dimethyl carbonate (0.3 M EC:DMC) and 0.5 M Ca(TFSI)2 dissolved in triglyme (0.5 M G3) have relatively small molar ratios of CIPs. The electrochemical performance was strongly related to the molar ratio of the CIPs. A high coulombic efficiency and high capacity were observed when using 0.3 M EC–DMC. Moreover, 0.5 M G3 showed the highest capacity despite its low coulombic efficiency. This could be related to the formation of solvent-separated ion pairs (SSIPs) due to the low polarity of G3 and its solvation form that encapsulates Ca2+. SSIPs had a reductively unstable character as that of the CIPs. Surface analysis revealed that the thinner the surface film produced, the lower the CIP content. This was deemed responsible for the rate performance enhancements, given the potential electrochemical instability of the Ca-containing CIPs.
Solid-State Electrochemical Synthesis of Silicon Clathrates Using a Sodium-Sulfur Battery Inspired Approach
Authors: Dopilka Andrew , Childs Amanda , Bobev Svilen , Chan Candace K.
Published: January 2021

Clathrates of Tetrel elements (Si, Ge, Sn) have attracted interest for their potential use in batteries and other applications. Sodium-filled silicon clathrates are conventionally synthesized through thermal decomposition of the Zintl precursor Na4Si4, but phase selectivity of the product is often difficult to achieve. Herein, we report the selective formation of the type I clathrate Na8Si46 using electrochemical oxidation at 450 °C and 550 °C. A two-electrode cell design inspired by high-temperature sodium-sulfur batteries is employed, using Na4Si4 as working electrode, Na β″-alumina solid electrolyte, and counter electrode consisting of molten Na or Sn. Galvanostatic intermittent titration is implemented to observe the oxidation characteristics and reveals a relatively constant cell potential under quasi-equilibrium conditions, indicating a two-phase reaction between Na4Si4 and Na8Si46. We further demonstrate that the product selection and morphology can be altered by tuning the reaction temperature and Na vapor pressure. Room temperature lithiation of the synthesized Na8Si46 is evaluated for the first time, showing similar electrochemical characteristics to those in the type II clathrate Na24Si136. The results show that solid-state electrochemical oxidation of Zintl phases at high temperatures can lead to opportunities for more controlled crystal growth and a deeper understanding of the formation processes of intermetallic clathrates.
Characterization of Artificial Pneumothorax-Unrelated Pyothorax-Associated Lymphoma
Authors: Chen Guang-Liang , Xia Zu-Guang , Jin Jia , Yu Bao-Hua , Cao Junning
Published: January 2021

Pyothorax-associated lymphoma (PAL) is a rare disease developing from a long-term pleural cavity inflammation. Most reported PAL cases have a history of artificial pneumothorax. However, the clinical features of artificial pneumothorax-unrelated PAL remain largely unknown. Here, we reported two PAL cases diagnosed from our center in the past ten years. One case developed from asymptomatic pyothorax after pneumonectomy with a latency of 28 years, while the other case showed a relatively short latency of one year. Then we reviewed the literature of artificial pneumothorax-unrelated PAL by searching PubMed and Google Scholar from 2007. In total, nine artificial pneumothorax-unrelated PAL cases were found, predominantly in old male with median age of 76 years (ranging from 51 to 88). Most cases were diagnosed with diffuse large B-cell lymphoma (DLBCL) (n = 8, 88.9%) and had evidence of Epstein-Barr virus (EBV) infection (n = 6, 66.7%) or tuberculous pleurisy (n = 5, 55.6%). Notably, four cases (44.4%) had short intervals (no more than two years) between pleuritis and PAL. Regarding the overall survival, one-third cases survived more than 5 years after the diagnosis of PAL. In conclusion, the features of artificial pneumothorax-unrelated PAL are comparable with the classic type of PAL, except for some patients with short duration of pleuritis, and need to be identified. Treatment guideline of DLBCL is recommended for the management of PAL.
Clinical Characteristics of Hypertensive Patients with Obstructive Sleep Apnoea Syndrome Developing Different Types of Left Ventricular Geometry
Authors: Myslinski Wojciech , Rekas-Wojcik Agata , Dybala Andrzej , Zakrzewski Maciej , Barud Wojciech , Prystupa Andrzej , Dzida Grzegorz , Bryl Wiesław , Mosiewicz Jerzy
Published: January 2021

Objective. The objective of the study was to compare polygraphic parameters and selected laboratory parameters in patients with obstructive sleep apnoea (OSA) who develop various types of left ventricular (LV) geometry. Material and Methods. The research covered 122 patients with obstructive sleep apnoea and coexisting effectively treated systemic hypertension (95 men, 27 women, average age: 54 ± 10.63). Overnight polygraphy, echocardiography, carotid artery ultrasonography, and laboratory measurements were performed. The patients were classified into four groups, depending on LV geometry. Group 1 comprised patients with normal LV geometry, group 2 included those with LV concentric remodelling. Group 3 and group 4 were patients with LV hypertrophy, concentric or eccentric, respectively. Results. The most frequent type of LV geometry in the examined population was eccentric hypertrophy (36%). The highest average values of BMI and T‐Ch were observed in the group of patients with concentric remodelling (group 2). The most severe respiratory disorders were found in the group of patients developing LV concentric hypertrophy (group 3); however, these differences were not statistically significant in comparison to other groups. Patients with LV eccentric hypertrophy had significantly decreased LV ejection fraction (p = 0.0008). Conclusions. LV eccentric hypertrophy is the most frequent type of LV geometry in OSA patients. Patients with severe sleep‐disordered breathing are more likely to develop concentric hypertrophy, while concentric remodelling occurs more frequently among OSA patients with other coexisting conditions, such as obesity or lipid‐related disorders.
Cross-Spectral Analysis of Electrocardiographic and Nostril Airflow Signals Identifies Two Respiratory Frequencies of Heart Rate Modulation
Authors: Lu Wan-An , Lin Jui-Feng , Wang Chen-Hsu , Chen Yung-Sheng , Shieh Ying-Hua , Kuo Cheng-Deng
Published: January 2021

Respiration is known to be a significant modulator of heart rate, and the high-frequency component in the power spectrum of heart rate variability (HRV) is believed to be caused mainly by respiration. To investigate the effect of respiration on heart rate, cross-spectral analysis of electrocardiographic (ECG) and nostril airflow signals was performed in healthy subjects to find the common features of ECG and respiration. Forty-two healthy subjects were included in this study. The autospectra of respective ECG and nostril airflow signals and the cross-spectra of ECG and nostril airflow signals were obtained and compared with the corresponding conventional HRV measures. We found that there were two spectral peaks at around 0.03 Hz and 0.3 Hz in the autospectrum of nostril airflow and the cross-spectrum of ECG and nostril airflow. In addition, the cross-spectral normalized high-frequency power (nHFPcs) was significantly larger than that of conventional HRV, while the cross-spectral normalized very low-frequency power (nVLFPcs), normalized low-frequency power (nLFPcs), and low-/high-frequency power ratio (LHRcs) were significantly lower than those of the conventional HRV. The cross-spectral nLFPcs and LHRcs had positive correlations with their corresponding HRV measures. We conclude that cross-spectral analysis of ECG and nostril airflow signals identifies two respiratory frequencies at around 0.03 Hz and below and around 0.3 Hz and can yield significantly enhanced nHFPcs and significantly suppressed nVLFPcs, as compared to their counterparts in conventional HRV. Both very low-frequency and high-frequency components of HRV are caused in part or mainly by respiration.
Parameter Detection of an On-Chip Embedded Debugging System of Wireless Sensor Internet Based on LEACH Algorithm
Authors: Zhou Ling-Ao
Published: January 2021

With the rapid development and maturity of unconnected communication technology, effector technology, embedded computing technology, and distributed information processing technology, as well as the rapid advancement of digital processing and computing capabilities, unconnected effector Internet has received more and more attention. It is a new type of self-organizing unconnected multihop Internet. With the development and progress of technology and society, the development of unconnected effector Internet is also advancing by leaps and bounds, and it has a wide range of applications in many fields such as military, civil, environmental, medical, and industrial. At present, the research on unconnected effector Internet mainly focuses on the communication protocol, but there is almost no research on input review of unconnected effector Internet. Due to the limited energy of the effector and the limitation of the transmission signal bandwidth, the use of limited resources for input review research in effector Internet is of great significance to the development of unconnected effector Internet. Therefore, this paper studies the input review of unconnected effector Internet based on the L-A model on the on-chip embedded tune system. Because the classic low-power adaptive cluster layering protocol (LEACH) has the problems of unbalanced energy consumption and short node life cycle, this paper uses the embedded tune technology based on the L-A model and analyzes the remaining energy and location of the unconnected effector Internet node. Parameters are tested and studied. Through the research on the input review of unconnected effector Internet, the simulation results obtained show that the research in this paper is feasible and reasonable.
A Novel Improved Reversible Visible Image Watermarking Algorithm Based on Grad-CAM and JND
Authors: Qu Jiasheng , Song Wei , Liu Xiangchun , Zhao Lizhi , Zhao Xiaobing
Published: January 2021

With the rapid access convenience of content brought by 5G technology, the integrity protection of content becomes more important. The reversible visible watermarking algorithm has attracted more attention due to its effective content protection. In this paper, a novel improved reversible visible image watermarking scheme based on gradient-weighted class activation mapping (Grad-CAM) and the just noticeable difference (JND) model has been presented. The proposed region of interest (ROI) selection strategy is used to locate the main protected body of images for watermark embedding. Divide the watermark and ROI into nonoverlapping blocks in the same way and then embed the classified two types of watermark blocks into corresponding ROI blocks with the JND model. The optimal bit positions for watermark embedding can be selected adaptively with JND threshold and achieve the tradeoff between the watermark visibility and watermarked image quality. For lossless image recovery and watermark extraction, the recovery information is reversibly hidden into watermarked image. In the experiments, the same process of grayscale images is used to each channel separately for color images watermarking. Besides, there are six aspects in this paper to estimate the proposed scheme; with the comparison to other reversible visible watermarking schemes, experimental results demonstrate the effectiveness of our proposed scheme.
Profit Maximization Model with Fare Structures and Subsidy Constraints for Urban Rail Transit
Authors: Wang Qing , Schonfeld Paul , Deng Lianbo
Published: January 2021

This paper analyzes government subsidies based on the service design (i.e., headway) and fare structures of an urban rail transit system while considering necessary financial support from the government. To capture the interactions among the operator performance, government subsidies, and passengers in an urban rail transit system, a profit maximization model with nonnegative profit constraint is formulated to determine the optimal fare and headway solutions. Then, the social welfare that results from the operator profit maximization model is analyzed. Finally, a numerical example from Changsha, China, is employed to verify the feasibility of the proposed model. The major results consist of optimized solutions for decision variables, i.e., the fares and train headways, as well as subsidies to the operator. The fare elasticity factor under two fare structures significantly affects fares and demand. As the fare elasticity factor increases, the social welfare gradually decreases and a deficit occurs at low fares and demand, while subsidies rise from 0 to ¥24658.00 and ¥38089.16 under the flat fare and distance-based fare structures.
Pet and Stray Dogs as Reservoirs of Antimicrobial-Resistant Escherichia coli
Authors: Marchetti Laura , Buldain Daniel , Gortari Castillo Lihuel , Buchamer Andrea , Chirino‐Trejo Manuel , Mestorino Nora
Published: January 2021

The close contact between dogs and humans creates the best bridge for interspecies transmission of antimicrobial-resistant bacteria. The surveillance of its resistance including the detection of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli as indicator bacteria is an important tool to control the use of antimicrobials. The aim of this research was to evaluate the E. coli resistance in strains by phenotypic methods, isolated from pet and stray dogs of La Plata city, Argentina. Faecal samples were collected using rectal swabs from 50 dogs with owners (home dogs = HD) and 50 homeless dogs (stray dogs = SD). They were cultured in 3 MacConkey agar plates, with and without antibiotics (ciprofloxacin and cefotaxime). 197 strains were isolated, of which only 95 strains were biochemically identified as E. coli, 46 strains were from HD, and 49 were from SD. Antimicrobial susceptibility was evaluated by the Kirby–Bauer disk diffusion method. The most prevalent resistance was for tetracycline, streptomycin, and ampicillin. In both groups, the level of resistance to 3rd generation cephalosporins was high, and there were multiresistant strains. There was a higher level of antimicrobial resistance in strains from SD compared to HD. There were 8% of strains suspected of being ESBLs among samples of HD and 36% of SD. One (2%) of the strains isolated from HD and 11 (22%) from SD were phenotypically confirmed as ESBL. Pets and stray dogs are a potential source of E. coli antibiotic resistance in Argentina; therefore, its surveillance must be guaranteed.
Efficacy of Early Endoscopic Ultrasound-Guided Transluminal Drainage for Postoperative Pancreatic Fistula
Authors: Fujimori Nao , Osoegawa Takashi , Aso Akira , Itaba Soichi , Minoda Yosuke , Murakami Masatoshi , Matsumoto Kazuhide , Teramatsu Katsuhito , Takamatsu Yu , Takaoka Takehiro , Oono Takamasa , Ihara Eikichi , Yoshizumi Tomoharu , Ohtsuka Takao , Nakamura Masafumi , Ogawa Yoshihiro
Published: January 2021

Background. Endoscopic ultrasound-guided transluminal drainage (EUS-TD) is generally performed 4 weeks after disease onset for evacuating pancreatic fluid collections. However, the optimal timing for conducting the procedure in those diagnosed with postoperative pancreatic fistula (POPF) has not been established. We aimed to elucidate the efficacy and safety of early EUS-TD procedures for treating POPF. Methods. We retrospectively reviewed patients diagnosed with POPF who underwent EUS-TD in the Kyushu University Hospital between 2008 and 2019. Clinical features were comparatively analyzed between the two patient groups who underwent either early (≤15 days postoperatively) or late (>15 days postoperatively) EUS-TD. Factors prolonging hospital stay were also analyzed using Cox proportional hazard models. Results. Thirty patients (median age, 64.5 years) were enrolled. The most common initial operation was distal pancreatectomy with splenectomy (60.0%). Median size of POPF was 69.5 (range, 38–145) mm, and median time interval between surgery and EUS-TD was 17.5 (range, 3–232) days. Totally, 47% patients underwent early EUS-TD. Rates of technical success, clinical success, and complications were 100%, 97%, and 6.9%, respectively. No recurrence of POPF occurred during a median follow-up period of 14 months. Clinical characteristics and outcomes were comparable between the early and late drainage patient groups, except for the rates of infection and nonencapsulation of POPF, which were significantly higher in the early drainage group. Performing simultaneous internal and external drainage (hazard ratio (HR): 0.31; 95% confidence interval (CI): 0.11–0.93,

p
=
0.04

) and conducting ≥2 treatment sessions (HR: 0.26; 95% CI: 0.08–0.84,

p
=
0.02

) were significantly associated with prolonged hospitalization after EUS-TD. Conclusions. EUS-TD is a safe and effective method for managing POPF, regardless of when it is performed in the postoperative period. Once infected POPF occurs, clinicians should not hesitate to perform EUS-TD even within 15 days of the initial operation.
Venoarteriovenous ECMO in Concomitant Acute Respiratory Distress Syndrome and Cardiomyopathy Associated with COVID-19 Infection
Authors: Bergman Zachary R. , Prathibha Saranya , Bauman Brent D. , Yannopoulos Demetris , Brunsvold Melissa E.
Published: January 2021

In the most severe cases, novel coronavirus (SARS-CoV-2) infection leads to Acute Respiratory Distress Syndrome which may be refractory to standard medical interventions including mechanical ventilation. There are growing reports of the use of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in these cases. A subset of critically ill COVID-19 patients develops cardiomyopathy as well, manifested by cardiogenic shock with reduced ejection fraction, dysrhythmias, and subsequent increase in mortality. One strategy for managing ARDS with an element of cardiogenic shock is venoarteriovenous (VAV) ECMO. Less than 1% of the cases in the worldwide ELSO COVID-19 database employed any form of hybrid cannulation. To date, there has only been one reported case of patient salvage with arterial or partial arterial support. We present a case that demonstrates the potential role of VAV ECMO in the case of concomitant severe ARDS with cardiomyopathy in the setting of COVID-19 infection.
Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma
Authors: Zhou Yaqi , Yang Weiqiang , Mei Xueshuang , Hu Hongyi
Published: January 2021

Background. Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis. Methods. mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40290) were selected. After all samples in each dataset were subjected to quality control using principal component analyses, the qualified samples were used for additional analyses. The genes that were significantly expressed in each dataset were intersected to identify the most significant of these. Gene functional enrichment analyses were performed on these genes, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. The protein–protein interaction network of selected genes was analyzed using the Search Tool for the Retrieval of Interacting Genes database. Significantly, differentially expressed genes were further verified with two RNA‐seq datasets (GSE68799 and GSE12452), as well as in clinical samples. Results. In all, 34 (8 upregulated genes and 26 downregulated) genes were identified as significantly differentially expressed. The immune response and the regulation of cell proliferation were the most enriched biological GO terms. Using reverse transcription quantitative real‐time PCR (RT‐qPCR), the genes MMP1, AQP9, and TNFAIP6 were detected to be upregulated, and FAM3D, CR2, and LTF were downregulated in NPC tissue samples. Conclusion. This study provides information on the genes that may be involved in the development of NPC and suggests possible druggable targets and biomarkers for diagnosing and evaluating the prognosis of NPC.
Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression
Authors: Barnabas Georgina D. , Lee Joo Sang , Shami Tamar , Harel Michal , Beck Lir , Selitrennik Michael , Jerby-Arnon Livnat , Erez Neta , Ruppin Eytan , Geiger Tamar
Published: January 2021

Cancer-specific metabolic phenotypes and their vulnerabilities represent a viable area of cancer research. In this study, we explored the association of breast cancer subtypes with different metabolic phenotypes and identified isocitrate dehydrogenase 2 (IDH2) as a key player in triple-negative breast cancer (TNBC) and HER2. Functional assays combined with mass spectrometry–based analyses revealed the oncogenic role of IDH2 in cell proliferation, anchorage-independent growth, glycolysis, mitochondrial respiration, and antioxidant defense. Genome-scale metabolic modeling identified phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) as the synthetic dosage lethal (SDL) partners of IDH2. In agreement, CRISPR-Cas9 knockout of PHGDH and PSAT1 showed the essentiality of serine biosynthesis proteins in IDH2-high cells. The clinical significance of the SDL interaction was supported by patients with IDH2-high/PHGDH-low tumors, who exhibited longer survival than patients with IDH2-high/PHGDH-high tumors. Furthermore, PHGDH inhibitors were effective in treating IDH2-high cells in vitro and in vivo. Altogether, our study creates a new link between two known cancer regulators and emphasizes PHGDH as a promising target for TNBC with IDH2 overexpression.

Significance:

These findings highlight the metabolic dependence of IDH2 on the serine biosynthesis pathway, adding an important layer to the connection between TCA cycle and glycolysis, which can be translated into novel targeted therapies.
Baseline Circulating Tumor Cell Count as a Prognostic Marker of PSA Response and Disease Progression in Metastatic Castrate-Sensitive Prostate Cancer (SWOG S1216)
Authors: Goldkorn Amir , Tangen Catherine , Plets Melissa , Morrison Gareth J. , Cunha Alexander , Xu Tong , Pinski Jacek K. , Ingles Sue A. , Triche Timothy , Harzstark Andrea L. , Kohli Manish , MacVicar Gary R. , Vaena Daniel A. , Crispino Anthony W. , McConkey David J. , Lara Primo N. , Hussain Maha H.A. , Quinn David I. , Vogelzang Nicholas J. , Thompson Ian Murchie , Agarwal Neeraj
Published: January 2021

Purpose:

In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC.

Experimental Design:

SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1–4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2–4.0 versus >4.0 (intermediate endpoint for overall survival); and progression-free survival (PFS) ≤ versus >2 years.

Results:

A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7–28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9–8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5.

Conclusions:

Baseline CTC count in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.
Use of Non-Selective Beta-Blocker for Refractory Stomal Variceal Hemorrhage
Authors: Mu Xin , Winsor Wendy , Trahey Julia
Published: January 2021

Bleeding stomal varices are often difficult to manage given the comorbidities that are associated with their presentation. Here, we report a case of a 62-year-old female with stomal variceal hemorrhage in the setting of chronic portal vein thrombosis who was ineligible for transhepatic intrajugular portosystemic shunt or surgery as a result of her challenging anatomy and peri-operative risks. Despite coil embolization, this patient experienced refractory bleeds which ceased following the initiation of a non-selective beta-blocker (NSBB). This case provides further evidence for the expanding role of NSBBs as an important therapeutic agent for complicated ectopic varices.
A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial of High-Dose, Short-Term Vitamin D Administration in the Prevention of Acute Kidney Injury after Cardiac Surgery
Authors: Eslami Pegah , Hekmat Manouchehr , Beheshti Mahmoud , Baghaei Ramin , Mirhosseini Seyed Mohsen , Pourmotahari Fatemeh , Ziai Seyed Ali , Foroughi Mahnoosh
Published: January 2021

Background: Acute kidney injury (AKI) after cardiac surgery is a relatively common complication affecting short- and long-term survival. The renoprotective effect of vitamin D (VitD) has been confirmed in several experimental models. This study was conducted to evaluate the effect of high-dose VitD administration in patients with VitD insufficiency on the incidence of postoperative AKI, the urinary level of tubular biomarkers, and serum anti-inflammatory biomarker after coronary artery bypass graft. Design and Method: In this randomized double-blind controlled clinical trial, the patients were randomly allocated to either the VitD group (n = 50), receiving 150,000 IU VitD tablets daily for 3 consecutive days before surgery or the control group (n = 61), receiving placebo tablets. Results: There was no difference in the incidence of postoperative AKI between the groups. Both of the urinary levels of interleukin-18 and kidney injury molecule-1 were significantly increased after the operation (p < 0.001, for both). Also, the serum level of interleukin-10 was increased after 3 days of VitD supplementation (p = 0.001). In comparison with the control group, it remained on a higher level after the operation (p < 0.001) and the next day (p = 0.03). The patients with AKI had more postoperative bleeding and received more blood transfusion. Conclusion: VitD pretreatment was unable to impose any changes in the incidence of AKI and the urinary level of renal biomarkers. However, high-dose administration of VitD may improve the anti-inflammatory state before and after the operation. Further studies are needed to assess the renoprotective effect of VitD on coronary surgery patients.
Cytogenetics of Four Species of the Green Clade Aplastodiscus Lutz, 1950 (Anura: Cophomantinae): New Insights into the Chromosomal Evolution of the Genus
Authors: Souza Késsia L. , Peixoto Marco A. , Barreto Cynthia A.V. , Feio Renato N. , Dergam Jorge A.
Published: January 2021

The tree frog Aplastodiscus is a Neotropical taxon that encompasses 15 species in the Atlantic forest biome, with one isolated species in the Central Brazilian Cerrado. To date, only 8 species have been karyotyped, showing high levels of diploid number variation, which allowed clustering species in chromosome number groups: 2n = 24 (Aplastodiscus perviridis group), 2n = 22 (Aplastodiscus albofrenatus group), 2n = 20, and 2n = 18 (both within Aplastodiscus albosignatus group). This study aims to report karyotypic information on 4 species from the last 2 groups using classical and molecular cytogenetic techniques and hypothesize chromosomal evolutionary trends within the species groups. Aplastodiscus weygoldti showed 2n = 22; Ag-NOR and FISH 18S rDNA signals were located in the interstitial region of the short arms of chromosome pair 6. Aplastodiscus cavicola, Aplastodiscus sp. 4, and Aplastodiscus sp. 6 showed 2n = 18; Ag-NOR and FISH 18S rDNA bands were located in the terminal region of the long arm of chromosome pair 9. Our results support multiple and independent chromosome fusion events within Aplastodiscus, including a new chromosome fission event. Ag-NOR and FISH 18S rDNA patterns were restricted to the small chromosome pairs, similar to the other species within this genus, and confirm overall chromosome morphology conservation among the genera of Cophomantinae.
Association of Physical Activity and Sitting Time with Overweight/Obesity in Chinese Occupational Populations
Authors: Yuan Fan , Gong Weiyan , Ding Caicui , Li Hui , Feng Ganyu , Ma Yanning , Fan Jing , Song Chao , Liu Ailing
Published: January 2021

Abstract: The aim of this study was to explore association of physical activity and sitting time with overweight/obesity in Chinese occupational populations for the development of intervention and prevention strategies for obesity. Methods: A total of 23,112 participants were selected from the 2010–2012 China National Nutrition and Health Survey (CNNHS). A logistics regression model was used to examine the associations of physical activity and sitting time with overweight/obesity by gender after adjusting for age, educational level, marital status, and family economic level. Results: The prevalence of overweight/obesity based on the WHO definition and the WGOC definition was 30.8% and 41.3%, respectively. Male employees with moderate and heavy occupation activity intensity had a lower risk for overweight/obesity than those with light occupation activity intensity (moderate: OR 0.90, 95% CI 0.82–0.98; heavy: OR 0.75, 95% CI 0.65–0.86), and the risk of overweight/obesity of male employees with long work-time spent sitting was higher than those with short work-time spent sitting (2–4.9 h/day: OR 1.26, 95% CI 1.14–1.40; ≥5 h/day: OR 1.29, 95% CI 1.15–1.44). The risk of overweight/obesity of male employees with active transportation mode was lower than those with inactive transportation mode (OR 0.91, 95% CI 0.84–0.99), while the risk of overweight/obesity of female employees with active transportation mode was higher (OR 1.14, 95% CI 1.04–1.25). Female employees with leisure-time physical activity (LTPA) for ≥150 min/week had lower risk of overweight/obesity than those with LTPA for <150 min/week (OR 0.69, 95% CI 0.56–0.84). There was no significant association of leisure-time sitting and housework time with overweight/obesity in Chinese occupational populations. Conclusion: Occupation activity intensity, LTPA, transportation mode, and work sitting time were associated with overweight/obesity. Reducing work sitting time, moderate and heavy occupation activity intensity, and an active transportation mode could help male employees decrease the risk of overweight/obesity. Increasing leisure-time physical activity could reduce the risk of overweight/obesity in women. Our findings provided insight into the association of physical activity and sitting time with overweight/obesity. It will be necessary to carry out workplace-based interventions, have an active transportation mode, and increase leisure-time physical activity to decrease the risks of overweight/obesity.
Follicular Granular Parakeratosis: A Case Report, Literature Review, and Proposed Classification
Authors: Chirasuthat Phatcharawat , Chirasuthat Suthep , Suchonwanit Poonkiat
Published: January 2021

Granular parakeratosis (GP) is a distinctive acquired keratotic dermatosis that is usually presented with brownish-red hyperkeratotic papules and plaques in the intertriginous areas. Follicular involvement in GP could be either extending lesions from interfollicular epithelium or originating primarily from the follicular epithelium. The latter was named follicular GP and is considered an extremely rare condition. To our knowledge, there has been one reported case so far in the literature. We herein report the second case of follicular GP in a 52-year-old Thai man presenting with multiple tiny filiform hyperkeratotic papules on his face 2 weeks after using anti-melasma cream. We also propose a classification of GP based on its distinct clinical manifestations and histopathological findings.
Probability of Prostate Cancer Diagnosis following Negative Systematic and Targeted MRI: Transrectal Ultrasound Fusion Biopsy: A Real-Life Observational Study
Authors: von Landenberg Nicolas , Hanske Julian , Noldus Joachim , Roghmann Florian , Tully Karl H. , Wald Jan , Berg Sebastian , Brock Marko
Published: January 2021

Introduction: The risk of occult prostate carcinoma (PCa) after negative multiparametric MRI (mpMRI)-transrectal fusion biopsy (F-Bx) is unknown. To determine the false-negative predictive value, we examined PCa detection after prior negative F-Bx. Methods: Between December 2012 and November 2016, 491 patients with suspected PCa and suspicious mpMRI findings underwent transrectal F-Bx. Patients with benign pathology (n = 191) were eligible for our follow-up (FU) survey. Patient characteristics and clinical parameters were correlated to subsequent findings of newly detected PCa. Results: Complete FU with a median of 31 (interquartile range: 17–39) months was available for 176/191 (92.2%) patients. Of those, 54 men had either surgical interventions on the prostate or re-Bxs. Newly detected PCa was evident in 14/176 (7.95%) patients stratified to ISUP ≤2 in 10 and ≥3 in 4 cases. The comparison of patients with newly detected PCa to those without cancerous findings in FU showed significant differences in prostate-specific antigen (PSA) density (0.16 vs. 0.13 ng/mL2) and prostate volume (45 vs. 67 mL, both p < 0.05). Both factors are significant predictors for newly detected cancer after initial negative F-Bx. Conclusion: Only PSA density (>0.13 ng/mL2) and small prostate volume are significant predictors for newly detected PCa after initial negative F-Bx. Despite negative mpMRI/TRUS F-Bx results, patients should be further monitored due to a risk of developing PCa over time. Notwithstanding the limitation of our study that not all patients underwent another Bx, we assume that the false-negative rate is low but existing. Our data represent a real-world scenario.
Klinischer Nutzen der Flüssigkeitsbiopsie beim uvealen Melanom
Authors: Seibel Ira
Published: January 2021

In the era of precision oncology, major strides are being made to use individual tumor information for clinical decision-making. Differing from traditional biopsy methods, the emerging practice of liquid biopsy provides a minimally invasive way of obtaining tumor cells and derived molecules. Liquid biopsy provides a means to detect and monitor disease progression, recurrence, and treatment response in a noninvasive way, and to potentially complement classical biopsy. Uveal melanoma (UM) is a unique malignancy, with diagnosis heavily reliant on imaging, few repeat biopsies, and a high rate of metastasis, which occurs hematogenously and often many years after diagnosis. In this disease setting, a noninvasive biomarker to detect, monitor, and study the disease in real time could lead to better disease understanding and patient care. While advances have been made in the detection of tumor-disseminated components, sensitivity and specificity remain important challenges. Ambiguity remains in how to interpret current findings and in how liquid biopsy can have a place in clinical practice. Related publications in UM are few compared to other cancers, but with further studies we may be able to uncover more about the biology of disseminated molecules and the mechanisms involved in the progression to metastasis.
The European Association for the Study of Obesity (EASO) Endorses the Milan Charter on Urban Obesity
Authors: Carruba Michele O. , Busetto Luca , Bryant Sheree , Caretto Antonio , Farpour-Lambert Nathalie J. , Fatati Giuseppe , Foschi Diego , Giorgino Francesco , Halford Jason C.G. , Lenzi Andrea , Malfi Giuseppe , O'Malley Grace , Napier David , Santini Ferruccio , Sbraccia Paolo , Spinato Chiara , Woodward Euan , Nisoli Enzo
Published: January 2021

The Milan Charter on Urban Obesity highlights the challenges of urban environments as a battleground for human health, as cities are often organized to subvert public health goals, and promote rather than prevent the development of obesity and consequent non-communicable diseases. The Charter articulates ten principles which detail actions and strategies through which general practitioners, diverse medical specialists, related healthcare professionals, administrators and healthcare practice managers, policy actors – within health systems and at a national level – along with experts across disciplines, and citizens, can work in cooperation to meet this challenge and improve public health. The Charter urges the adoption of decisions that deliver the following: (i) policies which enable our cities to become healthier and less obesogenic, more supportive of well-being and less health-disruptive in general, and (ii) policies that fully support primary prevention strategies, that address social stigma, and that ensure fair access to treatment for people living with obesity. The Milan Charter on Urban Obesity aims to raise awareness of our shared responsibility for the health of all citizens, and focuses on addressing the health of people living with obesity – not only as a challenge in its own right, but a gateway to other major non-communicable diseases, including cardiovascular diseases, type 2 diabetes, and some cancers.
Duplexsonographie bei Riesenzellarteriitis – Abschätzung von Schweregrad und möglicher Erblindung
Authors: Adler Sabine
Published: January 2021

Objectives: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. Methods: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. Results: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). Conclusion: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA.
Noncalcific Mechanisms of Bioprosthetic Structural Valve Degeneration
Authors: Marro Matteo , Kossar Alexander P. , Xue Yingfei , Frasca Antonio , Levy Robert J. , Ferrari Giovanni
Published: January 2021

Bioprosthetic heart valves (BHVs) largely circumvent the need for long‐term anticoagulation compared with mechanical valves but are increasingly susceptible to deterioration and reduced durability with reoperation rates of ≈10% and 30% at 10 and 15 years, respectively. Structural valve degeneration is a common, unpreventable, and untreatable consequence of BHV implantation and is frequently characterized by leaflet calcification. However, 25% of BHV reoperations attributed to structural valve degeneration occur with minimal leaflet mineralization. This review discusses the noncalcific mechanisms of BHV structural valve degeneration, highlighting the putative roles and pathophysiological relationships between protein infiltration, glycation, oxidative and mechanical stress, and inflammation and the structural consequences for surgical and transcatheter BHVs.
Reversion From Pre–Diabetes Mellitus to Normoglycemia and Risk of Cardiovascular Disease and All‐Cause Mortality in a Chinese Population: A Prospective Cohort Study
Authors: Liu Xiaoxue , Wu Shouling , Song Qiaofeng , Wang Xizhu
Published: January 2021

Background

It is unclear whether reversion from pre–diabetes mellitus to normoglycemia reduces cardiovascular disease (CVD) and all‐cause mortality risk in a Chinese population. We aimed to fill this research gap.

Methods and Results

The current study included 14 231 Chinese participants (mean age, 58.08 years) who were free from myocardial infarction and stroke at the time of survey participation (2006–2007 and 2008–2009). Participants were divided into 3 categories according to the 2‐year changes in pre–diabetes mellitus, defined by fasting plasma glucose: those with progression to diabetes mellitus, those with reversion from pre–diabetes mellitus to normoglycemia, and those with persistent pre–diabetes mellitus. Cox proportional hazards models were used to calculate hazard ratios (HRs) and their 95% CIs for CVD and all‐cause mortality. After a median follow‐up period of 8.75 years, a total of 879 CVD events (including 180 myocardial infarction events and 713 stroke events) and 941 all‐cause mortality events were recorded. After adjustment for confounding factors, reversion from pre–diabetes mellitus to normoglycemia was associated with decreased risks of CVD (HR, 0.78; 95% CI, 0.64–0.96), myocardial infarction (HR, 0.62; 95% CI, 0.40–0.97), stroke (HR, 0.79; 95% CI, 0.63–0.98), and all‐cause mortality (HR, 0.82; 95% CI, 0.68–0.99) compared with progression to diabetes mellitus.

Conclusions

Reversion from fasting plasma glucose–defined pre–diabetes mellitus to normoglycemia was associated with a reduction in the future risk of CVD and all‐cause mortality in a Chinese population.

Registration

URL:
https://www.chictr.org
; Unique identifier: ChiCTRTNC‐11001489.
The Regime of Islands Reframed:
Authors: Schofield Clive
Published: January 2021

The definition of islands represents a longstanding source of uncertainty under the international law of the sea, resulting in numerous disputes among coastal States. This is primarily due to the significant impacts the legal status of islands has on both their maritime entitlements and potential role in the delimitation of maritime boundaries. This study highlights the geographical diversity of islands and outlines the historical development of as well as progress towards the clarification of the legal definition of islands. The Award of the Arbitral Tribunal in the South China Sea case is examined in detail as it provides the first detailed international judicial examination and interpretation of the Regime of Islands. The definition of other types of insular features including low-tide elevations and artificial islands as well as submerged features are also addressed. Reactions to the interpretation of Article 121 by the Tribunal in the South China Sea case are explored before conclusions and considerations on the potential implications of these developments are offered.