bluuebunny/crossref_metadata_2025 huggingface dataset:
The Correlation between Matrix Metalloproteinase-9 Point-of-Care Immunoassay, Tear Film Osmolarity, and Ocular Surface Parameters
Authors: Kang Min-Ji , Kim Hyun Seung , Kim Man Soo , Kim Eun Chul
Published: April 2022

Background. Dry eye disease is a multifactorial disease that is difficult to diagnose due to multiple causative factors. The study aimed to evaluate the correlations between tear film matrix metalloproteinase-9 (MMP-9), tear film osmolarity, and ocular surface parameters in patients with dry eyes. Methods. We performed a retrospective chart review for patients diagnosed with dry eye and investigated if associations existed amongst noninvasive tear breakup time (NIBUT); corneal staining scores; and MMP-9 grade, tear film osmolarity, and Schirmer’s test I results. Results. Twenty-four eyes of 24 patients were enrolled in the current study. The grade of MMP-9 (0–4) was positively correlated with tear film osmolarity (

p
=
0.027

). However, neither qualitative (positive or negative) nor quantitative (grade 0–4) measurements of MMP-9 correlated with any other ocular surface parameters. The osmolarity in the positive corneal staining group was significantly higher than that in the negative group (321.6 ± 19.261 and 299.89 ± 16.213, respectively;

p
=
0.018

). None of the other ocular surface parameters were correlated with tear film osmolarity. Conclusion. Tear film MMP-9 may be an indicator for tear film osmolarity, or vice-versa. Moreover, osmolarity may have a correlation with corneal staining in patients with dry eye. Tear film MMP-9 and osmolarity tests can be helpful and convenient evaluation tools for identifying inflammation in dry eye disease in clinical practice.
An Overview of the Implications for Perianesthesia Nurses in terms of Intraoperative Changes in Temperature and Factors Associated with Unintentional Postoperative Hypothermia
Authors: Yang Fang , Wang Jing , Cui Jifang , Zhuan Jia , Hu Xiaoyan , Chen Shuting
Published: April 2022

Patients undergo surgery and anaesthesia on a daily basis across the United States and throughout the world. A major source of worry for these patients continues to be inadvertent hypothermia, once core temperature <36°C (96.8°F). Despite well-documented adverse physiological consequences, anaesthesia nurses continue to have a difficult task in keeping patient warmth pre-/peri-/post-surgical procedure. Thermostasis within postoperative patient necessitates the collaboration of many individuals. In order to provide safe and high-quality treatment, it is essential to use the most up-to-date data to guide therapeutic procedures targeted at achieving balance body temperature in surgical patients. Providing a review of the physiology of perioperative temperature variations and the comorbidities linked with accidental intraoperative hypothermia, this article will also provide preventive and treatment methods.
Pituitary Adenoma Surgery Survey: Neurosurgical Centers and Pituitary Adenomas
Authors: Netuka David , Grotenhuis Andre , Foroglou Nicolas , Zenga Francesco , Froehlich Sebastien , Ringel Florian , Sampron Nicolas , Thomas Nick , Komarc Martin , Majovsky Martin
Published: April 2022

Objective. Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers. Methods. A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice,” and geographical regions. Results. Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), <30 pituitary adenomas were operated per year. Twenty (7.9%) centers performed >100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%). Conclusions. In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe.
Parameter Sensitivity Analysis and Optimization of the Single-Layer Urban Canopy Model in the Megacity of Shanghai
Authors: Ao Xiangyu , Zhang Ning
Published: April 2022

In order to meet the demand of more refined urban weather forecast, it is of great practical significance to improve and optimize the single-layer urban canopy model (SLUCM) suitable for the megacity of Shanghai. In this paper, based on the offline SLUCM model driven by a whole-year surface flux observation data in the Shanghai central business district, a series of parameter sensitivity tests are carried out by using the one at a time (OAT) method, the relative importance and a set of optimized parameters of the SLUCM suitable for high-density urban area are established, and the improvement of simulation is evaluated. The results show that SLUCM well reproduces the seasonal mean diurnal patterns of the net all-wave radiation flux (

Q

∗

) and sensible heat flux (QH) but underestimates their magnitudes. Both

Q

∗

and QH are linearly sensitive to the albedo, and most sensitive to the roof albedo, the second to the wall albedo, but relatively insensitive to the road albedo. The sensitivity of

Q

∗

and QH to emissivity is not as strong as that of albedo, and the variation trend is also linear. Similar to albedo,

Q

∗

and QH are most sensitive to roof emissivity. The effect of thermal parameters (heat capacity and conductivity) on fluxes is logarithmic. The sensitivity of surface fluxes to geometric parameters has no specific variation pattern. After parameter optimization, RMSE of

Q

∗

decreases by about 3.4–18.7 Wm−2 in four seasons. RMSE of the longwave radiation (L↑) decreases by about 1.2–7.87 Wm−2. RMSE of QH decreases by about 2–5 Wm−2. This study provides guidance for future development of the urban canopy model parameterizations and urban climate risk response.
Comprehensive Review of Community Seismic Resilience: Concept, Frameworks, and Case Studies
Authors: Chee Yin H’ng , Kassem Moustafa Moufid , Mohamed Nazri Fadzli
Published: April 2022

Seismic resilience is a concept to evaluate the postearthquake functionality of structures that significantly play a critical role in postearthquake rescue and recovery. Indeed, the community is made up of more than just buildings; it is also made up of other subsystems such as hospital and school facilities as well as roads, drainage systems, sewer systems, and electrical power transmission networks. In recent years, the concept of community resilience as a tool for disaster risk management has attracted substantial attention from all parties, such as governments, designers, decision‐makers, and stakeholders. Community resilience can be assessed more effectively by using a multi‐disciplinary approach that takes into account the community’s uncertainties, as opposed to a single‐criteria approach. The global community resilience model must be long‐term validated and dependent on the most vulnerable and low‐resilience portions of the community, according to a prior study. According to the review of the seismic resiliency studies performed in the recent decades, the frameworks for the quantification assessment of the community resilience are explained. Moreover, several case studies for community resilience and the application of different subsystems are reviewed and elaborated in this paper. Based on these resilience studies, the main challenges on the effectiveness of the resilience assessment are the availability and accessibility of the data, the financial resources, and the cooperation from all the parties.
Juvenile Hemochromatosis due to a Homozygous Variant in the HJV Gene
Authors: Moreno-Risco María-Belén , Méndez Manuel , Moreno-Carralero María-Isabel , López-Moreno Ana-María , Vagace-Valero José-Manuel , Morán-Jiménez María-José
Published: April 2022

Hemochromatosis type 2 or juvenile hemochromatosis has an early onset of severe iron overload resulting in organ manifestation such as liver fibrosis, cirrhosis, cardiomyopathy, arthropathy, hypogonadism, diabetes, osteopathic medicine, and thyroid abnormality, before age of 30. Juvenile hemochromatosis type 2a and 2b is an autosomal recessive disease caused by pathogenic variants in HJV and HAMP genes, respectively. We report a child with hepatic iron overload and family history of hemochromatosis. We aim to raise awareness of juvenile hemochromatosis, especially in families with a positive family history, as early diagnosis and treatment may prevent organ involvement and end-stage disease. The purpose of this study was to identify the gene variant that causes the disease. The genetic study was performed with a targeted gene panel: HFE, HJV, HAMP, TFR2, SLC40A1, FTL, and FTH1. We identified the variant c.309C > G (p.Phe103Leu) in the HJV gene in the homozygous state in the patient.
Risk Analysis of Positive PD-L1 Expression and Clinicopathological Features and Survival Prognosis in Patients with Colorectal Cancer: Systematic Review and Meta-Analysis
Authors: Tang Maocai , Zheng Ziling , Shang Jingkun , Zhang Shouru
Published: April 2022

In order to explore the significance of PD-L1 expression in the prognosis and clinicopathological characteristics of colorectal cancer (CRC), the PubMed, Embase, Web of Science, Cochrane Library, CNKI, and multisquare databases are systematically searched for the relevant relationship between PD-L1 expression and CRC prognosis. The search time is completed until June 2021. Literature is filtered and data extracted by inclusion exclusion criteria, and Meta-analysis is performed with Stata SE12.0 software. 16 documents are included, and a total of 1997 CRC patients are included. The results show that recurrence-free survival (RFS) [OR = 2.69, 95%CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50), and disease-free survival (DFS) (OR = 3.71, 95% CI (2.32,5.93), P < 0.00001, I2 = 37%, Z = 5.48) and PD-L1 expression and tumor differentiation (OR = 4.00, 95%CI (2.97,5.38), P < 0.00001, I2 = 0%, Z = 9.11) and lymphatic action metastasis (OR = 2.69,95% CI (2.07,3.48), P < 0.00001, I2 = 0%, Z = 7.50) is significantly associated.PD-L1 expression in tumor tissue suggests a poor prognosis in colorectal cancer, and the predictive significance of PD-L1 expression and PD-L1 expression in tumor cells in tumor-infiltrating immune cells may be inconsistent.
Control Measures for Automobile Exhaust Emissions in PM2.5 Governance
Authors: Qin Dong-Sheng , Gao Chang-Yuan
Published: April 2022

This paper analyses the correlation between automobile exhaust, PM2.5, and air pollution to explore the rate of contribution of automobile exhaust to PM2.5 pollution and the effect of government regulation on automobile exhaust gas. The results show that the atmosphere is hazy and that car exhaust is the main cause of PM2.5 pollution. This paper divides the governance strategy into two methods: reducing the number of motor vehicles and reducing the emissions capacity of motor vehicles. It also analyses the effects of congestion control on public car travel and establishes a dynamic game model. To strengthen the influence of supervision on enterprises with regard to purifying devices and restrictions, this study also creates a “prisoner’s dilemma” model. The final results of the study show that restriction measures can effectively relieve road pressure. Additionally, congestion costs can alleviate environmental pressure, but it is difficult to determine the costs, and the difficulty of implementation increases. Increasing enterprises’ installation of purifying devices is not advisable or desirable in the short term. Finally, the paper offers some suggestions for the maintenance of the atmospheric environment and the management of automobile exhaust: (1) improve the national green transport system and environmental protection awareness; (2) advocate public transport as a mode of travel; and (3) reduce the use of buses and popularize new energy vehicles.
An Unusual TEN-Like Presentation of Juvenile Bullous Pemphigoid: A Diagnostic Challenge
Authors: Nikyar Zahra , Hatami Parvaneh , Aryanian Zeinab , Sotoudeh Soheila , Ziaee Vahid , Goodarzi Azadeh
Published: April 2022

Bullous pemphigoid (BP) is an acquired autoimmune bullous disorder rarely seen in the pediatric population. It usually presents as large and tense bullae, predominantly distributed in the acral areas. Herein, we describe a case of childhood BP with an atypical presentation mimicking toxic epidermal necrolysis (TEN). This case shows us that juvenile BP should be considered in the differential diagnosis of TEN in children, particularly if there are unusual features and an intractable course.
Long-Term Sustainability and Multifractal Characteristics of Air Pollution Evolution
Authors: Antao Wang , Linan Sun
Published: April 2022

Air pollution is a complex phenomenon caused by humans causing certain substances to enter the atmosphere during production activities or natural processes. Its formation and evolution have long-term sustainability, macroscopicity, and integrity. The concentration of each pollutant is high or low, and it will last for a period of time. So, what are the macro and overall characteristics of the self-evolution of the concentration of each pollutant? This article will use the detrended fluctuation analysis (DFA) method to analyze the long-term sustainability of each pollutant concentration sequence at nine sites. At the same time, in order to describe the nonlinear characteristics of each pollutant concentration sequence in more detail, use the multifractal detrended fluctuation analysis (MF-DFA) method to analyze the internal local structure. The MF-DFA method can describe the unique mode of the pollution process during the haze period, record the detailed information of the pollutants on different time scales during the haze period, provide probability estimates for the pollutant concentration, and display the pollutant concentration. The MF-DFA method can also describe the characteristics of time series in a more detailed, precise, and comprehensive manner and quantitatively describe the long-term sustainability of time series evolution. The experimental analysis results of the MF-DFA method on the concentration of each pollutant at nine monitoring points during the haze period have achieved extraordinary results.
Enamel Matrix Derivatives for Periodontal Regeneration: Recent Developments and Future Perspectives
Authors: Fan Liping , Wu Dan
Published: April 2022

In the era of the growing population, the demand for dental care is increasing at a fast pace for both older and younger people. One of the dental diseases that has attracted significant research is periodontitis. Periodontal therapy aims to regenerate tissues that are injured by periodontal disease. During recent decades, various pioneering strategies and products have been introduced for restoring or regeneration of periodontal deficiencies. One of these involves the regeneration of tissues under guidance using enamel matrix derivatives (EMDs) or combinations of these. EMDs are mainly comprised of amelogenins, which is one of the most common biological agents used in periodontics. Multiple studies have been reported regarding the role of EMD in periodontal tissue regeneration; however, the extensive mechanism remains elusive. The EMDs could promote periodontal regeneration mainly through inducing periodontal attachment during tooth formation. EMD mimics biological processes that occur during periodontal tissue growth. During root development, enamel matrix proteins are formed on the root surface by Hertwig’s epithelial root sheath cells, initiating the process of cementogenesis. This article reviews the challenges and recent advances in preclinical and clinical applications of EMDs in periodontal regeneration. Moreover, we discuss the current evidence on the mechanisms of action of EMDs in the regeneration of periodontal tissues.
m6A-Related lncRNAs Are Potential Prognostic Biomarkers of Cervical Cancer and Affect Immune Infiltration
Authors: Jia Haixia , Hao Suhua , Cao Meiting , Wang Lifang , Bai Hua , Shui Wen , Yang Xiaotang
Published: April 2022

The correlation of m6A-related lncRNAs with the prognosis and immune microenvironment of cervical cancer is not yet clear. In this study, we identified 7 m6A-related prognostic lncRNAs by Pearson correlation and univariate Cox regression analyses based on TCGA-cervical cancer dataset. Then, patients were divided into two clusters by consensus clustering based on the 7 m6A-related prognostic lncRNA expression. Cluster 1 was characterized by survival and stage disadvantage, enrichment of immunosuppressive and carcinogenic activation pathways. Besides, cluster 1 had higher immunosuppressive factor TGFbeta and lower immune cell infiltration compared with cluster 2. According to the expression of 7 m6A-related lncRNA, a 6-m6A-related lncRNA risk score model was established in the training set by LASSO regression analysis. The high-risk group had worse overall survival than the low-risk group. No matter in the training or validation sets, the m6A-related lncRNA risk score was an independent prognostic factor for overall survival. Meanwhile, we validated the independent prognostic value of risk score in the disease-specific survival and progression-free survival by multivariate Cox analysis. The high-risk group was characterized by higher TGFbeta and regulatory T cell and was rich in malignant pathways. Additionally, we also detected and compared the expression levels of four m6A-related prognostic lncRNA in 9 tumor samples and 9 normal tissues using quantitative real-time polymerase chain reaction assay. In conclusion, the novel m6A-related lncRNA risk score is a potential prognostic predictor of cervical cancer patients. These 6 m6A-related lncRNAs might serve as key mediators of the immune microenvironment and represent promising therapeutic targets for improving cervical cancer prognosis.
Design and Evaluation of the Interface of Recreational Intelligent Escort Products
Authors: Han Xu , Jiao Lulu , Tan Baohua , Tian Fang , Zhao Wenbin , Yu Hua
Published: April 2022

In the context of the Internet of Things (IoT), the user interface has become the main means of interaction between the user and the network system, and the increasing variety of ways of interacting with the user interface has created many “digital problems” for the elderly. In order to explore the preferences of elderly people in using smart products and to help designers to objectively and rationally select interface design solutions, to enhance the experience of elderly people in using smart products and the naturalness of the interaction process, and to motivate them to actively participate in Internet life, this study proposes a new approach to interface design solution selection, which reduces the subjectivity of solution selection in the design process. Firstly, the interface was decomposed into 7 components, and the orthogonal experimental design was used to calculate the evaluation indexes and the correlation degree between the objects of 18 typical solutions, and finally the preferred solution was obtained. Secondly, conjoint analysis was used to obtain the importance that older users attached to the seven interface components and their preferences for the types of elements. The research takes the interface design of an elderly companion robot as an example. The method enables the optimization of the target problem of how to match the interface design elements and the final solution preference in IoT systems, enabling designers to use mathematical and rational thinking to study contradictory problems, enhancing the objectivity and scientificity of interface design and solution selection, providing a more natural and comfortable interaction experience for elderly users, and promoting healthy ageing.
A Comparative Study on the Diagnostic Value of CTA and MRA in Anterior Dislocation of Shoulder
Authors: Wu Junhua , Zhang Tao , Li Xuxue , Dan Qian , Zhang Dezhou
Published: April 2022

Objective. To investigate the diagnostic value of CTA and MRA in anterior dislocation of shoulder. Methods. The detection of inferior glenohumeral ligament injuries, anterior inferior labrum injuries, and bone and cartilage injuries by the two examination procedures was observed and compared with the results of arthroscopy or surgery on patients referred to our hospital owing to anterior dislocation of shoulder. Results. A total of 36 patients with shoulder injuries were gathered for this study. 32 cases with anterior inferior labrum tearings (27 cases detected by CTA and 30 cases by MRA), 24 cases with inferior glenohumeral ligament tearings (14 cases detected by CTA and 22 cases by MRA), 24 cases with inferior glenohumeral ligament tearings (14 cases detected by CTA and 22 cases by MRA), and 24 cases with inferior glenohumeral ligament tearings (14 cases detected by CTA and 22 cases by MRA) were detected. There were 30 bone and cartilage injuries, including 18 fractures (CTA identified 18), 10 bone contusions (CTA detected 0), and 5 cartilage damage (CTA detected 0) (CTA detected 0, MRA detected 5). Conclusion. The detection rate of MRA is better than that of CTA for inferior glenohumeral ligament injuries. For anterior inferior labrum injury, the detection rate of CTA and MRA was similar. CTA is more conducive to the detection of fracture blocks, while MRA is more advantageous for the observation of bone contusion and cartilage damage.
Factors Influencing Teaching Quality in Universities: Analyzing Causal Relationships Based on Neutrosophic DEMATEL
Authors: Mamites Irene , Almerino Porferio , Sitoy Regina , Atibing Nadine May , Almerino Jana Gloria , Cebe Danilo , Ybañez Ricardo , Tandag Jemima , Villaganas Mary Anne , Lumayag Charisma , Plando Dennis , Añero Marjorie , Acebes Harlene Marie , Maturan Fatima , Evangelista Samantha Shane , Aro Joerabell Lourdes , Himang Celbert , Ocampo Lanndon
Published: April 2022

While teaching quality has been widely studied, this work advances the domain literature by evaluating the factors influencing teaching quality in order to determine their causal relationships and eventually identify those crucial factors. With ten factors obtained from a comprehensive review of literature, the neutrosophic decision-making trial and evaluation laboratory (DEMATEL) method is used to model these factors in the case of public universities in the Philippines. The DEMATEL handles the causal relationships among factors of teaching quality, while the vagueness associated with domain experts eliciting judgments within the DEMATEL is modeled in single-valued neutrosophic numbers. Findings reveal that individual characteristics, psychological characteristics, and institutional culture are key factors of teaching quality, while institutional resources and student composition are minor key factors. Higher education institutions (HEIs) must pay more attention to these factors in designing different initiatives, as they are crucial in shaping teaching quality. These findings offer important insights for HEIs in their recruitment and hiring decisions, strategic road mapping for building an institutional culture that values teaching quality, establishing student composition schemes, and resource allocation decisions for promoting institutional resources that drive teaching quality initiatives. Some policy takeaways and avenues for future works are also discussed.
The Combination of 18F‐Fluorodeoxyglucose Positron Emission Tomography Metabolic and Clinical Parameters Can Effectively Distinguish Rheumatoid Arthritis and Polymyalgia Rheumatic
Authors: Wang Guanyun , Liu Xiaofei , Chen Jiaxin , Zhang Fengyan , Xu Xiaodan , Wang Yanmei , Wang Ruimin , Yao Shulin , Zhu Jian , Guan Zhiwei
Published: April 2022

Objective. To evaluate 18F‐fluorodeoxyglucose positron emission tomography (18FDG PET) and clinical parameters to differentiate rheumatoid arthritis (RA) and polymyalgia rheumatic (PMR). Patients and Methods. This retrospective study evaluated 54 patients with suspected RA (n = 23) and PMR (n = 31) who underwent 18F‐FDG PET/CT before treatment. The complete diagnosis was based on each classification criterion and at least followed up for 6 months. Demographic and clinical data were also collected. Semiquantitative analysis (maximum standardized uptake value, SUVmax) of abnormal 18F‐FDG uptake was undertaken at 17 musculoskeletal sites, and two scoring systems (mean reference (liver/control) scores) were evaluated. The differential diagnostic efficacy of each independent parameter was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and bootstrap tests were used to evaluate the improvement in diagnostic efficacy using a combination of multiple parameters. Results. The ROC curve analysis of SUVmax indicated that the interspinous ligament showed the highest discriminative diagnostic value (sensitivity, 64.5%; specificity, 78.3%; area under the curve (AUC), 0.764; positive predictive value, 0.800; negative predictive value, 0.621). The combined model with the rheumatoid factor (RF) and metabolic parameters of 18F‐FDG PET resulted in the highest AUC of 0.892 and showed significant reclassification by IDI (IDI, 9.51%; 95% confidence interval: 0.021–0.175; P = 0.013). According to the bootstrap test, compared with RF alone, the combination of RF and metabolic parameters showed an improvement in ROC and was statistically significant (P = 0.017). Conclusions. The combination of 18F‐FDG PET metabolic and clinical parameters can further improve the differential diagnosis of RA and PMR.
New Control Approach of Multicell Stacked Cell Inverter for Solar Photovoltaic System
Authors: Yonga François , Welba Colince , Dadjé Abdouramani , Djongyang Noël
Published: April 2022

This paper presents the study, modelling, and simulation of the DCSVM (Duty Cycle Space Vector Modulation) control technique applied to a new inverter topology dedicated to isolated or grid-connected photovoltaic systems using the MATLAB/Simulink software. This inverter is based on the structures of a stacked multicell converter (SMC) and an H-bridge. This new topology allows the voltage stresses of the converter to be distributed among several switching cells. It also allows the input voltage to be divided into several fractions so that the number of switching power semiconductors is reduced. The DCSVM is a control technique that generates control signals to the two-level voltage converter as well as the intermediate times. The main advantage of this control technique is the reduction in the number of calculations, especially for the trigonometric functions and the generation of the reference voltage. In this contribution, the general topology of this microinverter is described and the DCSVM control technique is presented. Finally, simulation results, the efficiency of this topology, and the validity of the DCSVM control in a grid-connected PV generation system are discussed. The results obtained are very satisfactory.
Delayed Administration of Nintedanib Ameliorates Fibrosis Progression in CG-Induced Peritoneal Fibrosis Mouse Model
Authors: Cui Binbin , Yu Chao , Zhang Shenglei , Hou Xiying , Wang Yi , Wang Jun , Zhuang Shougang , Liu Feng
Published: April 2022

Background: A multiple-target tyrosine kinase inhibitor, nintedanib, which is approved for treatment of interstitial pulmonary disease, has been demonstrated to have anti-fibrotic activity outside of the lungs. We explored its therapeutic effect in a murine model of peritoneal fibrosis. Methods: Daily intraperitoneal injections of chlorhexidine gluconate (CG) induced peritoneal fibrosis in mice. The effects of delayed administration of nintedanib (given at day 21 after CG injection and then given daily for 14 days) were determined by immunohistochemical staining, ELISA, and immunoblot analysis. Results: Delayed administration of nintedanib significantly inhibited peritoneal fibrosis progression as indicated by decreasing deposition and expression of extracellular matrix (ECM) proteins (fibronectin and type I collagen). Treatment with nintedanib also upregulated MMP-2 and reciprocally downregulated TIMP-2, along with reducing expression of α-SMA, β-vimentin, and two transcription factors (Snail and Twist), and retaining E-cadherin expression. Nintedanib also inhibited co-expression of β-vimentin with Snail or Twist as shown by immunofluorescent staining. Moreover, nintedanib decreased the number of CD31-positive blood vessels and CD31 expression in the injured peritoneum. Moreover, delayed application of nintedanib inhibited the expression of several cytokines/chemokines, including monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6, and infiltration of CD68+ macrophages to the injured peritoneum. Finally, nintedanib blocked phosphorylation of STAT3, NF-κB, and Smad3 during the development of peritoneal fibrosis. Conclusions: Delayed administration of nintedanib inhibits progression of peritoneal fibrosis and partially reverses established peritoneal fibrosis by attenuating epithelial-mesenchymal transition, inflammation, and angiogenesis, as well as promoting ECM degradation. We conclude that nintedanib has a therapeutic potential to treat peritoneal fibrosis.
Is Polymerase Chain Reaction Positivity More Common in Patients with COVID-19 Pneumonia with Fever?
Authors: Cireli Emel , Mertoğlu Aydan , Balcı Günseli , Bayram Aylin , Kuranoğlu Nil , Çırak Ali Kadri
Published: April 2022

Introduction: There is conflicting data about the rate of fever at admission and during hospitalization in COVID-19 pneumonia. We analyzed the rate of fever in our patients to find the diagnostic value of fever and to predict PCR status in COVID-19. Methods: It was a retrospective cross-sectional study conducted in the Health Sciences University Dr. Suat Seren Chest Diseases and Chest Surgery Training and Research Hospital, which was a tertiary chest diseases pandemic hospital in İzmir. We included 389 patients hospitalized for COVID-19 and analyzed them according to PCR status and presence of fever. Fever was defined as temperature over 38°C. Results: Thirty-eight percentage of our patients complained of fever before admission. However, when they were admitted, only 13.6% of them had objective high fever. 26.5% had high fever during hospital stay. PCR-positive patients had less comorbidity. More of PCR-positive patients had fever in the course of hospitalization and their length of hospital stay was longer and mortality was higher. Although we expected to find a high sensitivity, the sensitivity of high fever in our settings was low. Sensitivity, specificity, positive, and negative predictive values of high fever at admission in predicting the positivity of the PCR test were 16.9%, 90.6%, 69.8%, and 45.8%, respectively. Sensitivity, specificity, positive, and negative predictive values of high fever during hospitalization to predict the positivity of PCR test were 36.1%, 85.9%, 76.7%, and 51.0%, respectively. Conclusion: 13.6% of our COVID-19 patients had objective high fever at admission. 26.5% had high fever during hospital stay. PCR-positive patients had less comorbidity. More PCR-positive patients had fever in the course of hospitalization and their length of hospital stay was longer and mortality was higher. Although we expected to find a high sensitivity, the sensitivity of high fever in our settings was lower than expected. Temperatures <38°C at admission and during hospitalization determine 90.6% and 85.9% of the PCR-negative patients, respectively. These high specificity values imply that if the PCR test is negative, the patient’s temperature is more likely to be lower than 38°C.
Impact of Diabetes on Patient Outcomes in Breast Cancer Patients
Authors: Tobe Akiko , Horimoto Yoshiya , Kobayashi Kazuki , Kamisada Nozomi , Hirano Minoru
Published: April 2022

Background: Diabetes and the etiology of breast cancer are clearly associated. However, the impact of diabetes on prognosis is not yet understood. Therefore, we conducted a retrospective cohort study to examine the relationship between diabetes and patient outcomes in breast cancer patients. Methods: We investigated 332 Japanese women with breast cancer who underwent curative surgery at our hospital. Patients without sufficient clinical information including hemoglobin A1c (HbA1c) and those with an observation period of less than 1 year were excluded. Results: Among the patients examined, 106 had diabetes at the time of their breast cancer diagnosis. Among the 296 patients with invasive breast carcinoma, 36 patients developed distant metastases during the mean observation period of 45 months. Sixteen patients died due to breast cancer, while 13 died of other causes. Multivariate analysis revealed that diabetes, tumor size, and estrogen receptor (ER) status were independent factors related to distant metastasis-free survival (DMFS) (p = 0.038, p < 0.001, and p = 0.006, respectively). Kaplan-Meier curve analysis revealed that diabetes negatively affected the outcomes of ER-negative breast cancer patients both in DMFS and overall survival (p = 0.045 and p = 0.029, respectively). Meanwhile, patient outcomes did not differ according to the level of HbA1c in diabetes patients. Conclusion: Patients with diabetes had a significantly shorter DMFS, and the negative effect of diabetes on patient outcomes was more evident in ER-negative breast cancer. Our data indicates the importance of primary prevention of diabetes for breast cancer patients.
Myeloid Cell PKM2 Deletion Enhances Efferocytosis and Reduces Atherosclerosis
Authors: Doddapattar Prakash , Dev Rishabh , Ghatge Madankumar , Patel Rakesh B. , Jain Manish , Dhanesha Nirav , Lentz Steven R. , Chauhan Anil K.
Published: April 2022

Background:

The glycolytic enzyme PKM2 (pyruvate kinase muscle 2) is upregulated in monocytes/macrophages of patients with atherosclerotic coronary artery disease. However, the role of cell type-specific PKM2 in the setting of atherosclerosis remains to be defined. We determined whether myeloid cell-specific PKM2 regulates efferocytosis and atherosclerosis.

Methods:

We generated myeloid cell-specific PKM2
−/−
mice on Ldlr (low-density lipoprotein receptor)-deficient background (PKM2
mye-KO
Ldlr
−/−
). Controls were littermate PKM2
WT
Ldlr
−/−
mice. Susceptibility to atherosclerosis was evaluated in whole aortae and cross sections of the aortic sinus in male and female mice fed a high-fat Western diet for 14 weeks, starting at 8 weeks.

Results:

PKM2 was upregulated in macrophages of Ldlr
−/−
mice fed a high-fat Western diet compared with chow diet. Myeloid cell-specific deletion of PKM2 led to a significant reduction in lesions in the whole aorta and aortic sinus despite high cholesterol and triglyceride levels. Furthermore, we found decreased macrophage content in the lesions of myeloid cell-specific PKM2
−/−
mice associated with decreased MCP-1 (monocyte chemoattractant protein 1) levels in plasma, reduced transmigration of macrophages in response to MCP-1, and impaired glycolytic rate. Macrophages isolated from myeloid-specific PKM2
−/−
mice fed the Western diet exhibited reduced expression of proinflammatory genes, including MCP-1, IL (interleukin)-1β, and IL-12. Myeloid cell-specific PKM2
−/−
mice exhibited reduced apoptosis concomitant with enhanced macrophage efferocytosis and upregulation of LRP (LDLR-related protein)-1 in macrophages in vitro and atherosclerotic lesions in vivo. Silencing LRP-1 in PKM2-deficient macrophages restored inflammatory gene expression and reduced efferocytosis. As a therapeutic intervention, inhibiting PKM2 nuclear translocation using a small molecule reduced glycolytic rate, enhanced efferocytosis, and reduced atherosclerosis in Ldlr
−/−
mice.

Conclusions:

Genetic deletion of PKM2 in myeloid cells or limiting its nuclear translocation reduces atherosclerosis by suppressing inflammation and enhancing efferocytosis.
Computational Analysis of Routine Biopsies Improves Diagnosis and Prediction of Cardiac Allograft Vasculopathy
Authors: Peyster Eliot G. , Janowczyk Andrew , Swamidoss Abigail , Kethireddy Samhith , Feldman Michael D. , Margulies Kenneth B.
Published: April 2022

Background:

Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality for heart transplant recipients. Although clinical risk factors for CAV have been established, no personalized prognostic test exists to confidently identify patients at high versus low risk of developing aggressive CAV. This investigation aimed to leverage computational methods for analyzing digital pathology images from routine endomyocardial biopsies (EMBs) to develop a precision medicine tool for predicting CAV years before overt clinical presentation.

Methods:

Clinical data from 1 year after transplant were collected on 302 transplant recipients from the University of Pennsylvania, including 53 patients with early-onset CAV and 249 no early-onset CAV controls. These data were used to generate a clinical model (Clinical Risk Factor Future Cardiac Allograft Vasculopathy Prediction Model [ClinCAV-Pr]) for predicting future CAV development. From this cohort, 183 archived EMBs were collected for CD31 and modified trichrome staining and then digitally scanned. These included 1-year posttransplant EMBs from 50 patients with early-onset CAV and 82 patients with no early-onset CAV, as well as 51 EMBs from disease control patients obtained at the time of definitive coronary angiography confirming CAV. Using biologically inspired, handcrafted features extracted from digitized EMBs, quantitative histological models for differentiating no early-onset CAV from disease controls (Histological Cardiac Allograft Vasculopathy Diagnostic Model [HistoCAV-Dx]) and for predicting future CAV from 1-year posttransplant EMBs were developed (Histological Future Cardiac Allograft Vasculopathy Prediction Model [HistoCAV-Pr]). The performance of histological and clinical models for predicting future CAV (ie, HistoCAV-Pr and ClinCAV-Pr, respectively) were compared in a held-out validation set before being combined to assess the added predictive value of an integrated predictive model (Integrated Histological/Clinical Risk Factor Future Cardiac Allograft Vasculopathy Prediction Model [iCAV-Pr]).

Results:

ClinCAV-Pr achieved modest performance on the independent test set, with an area under the receiver operating curve (AUROC) of 0.70. The HistoCAV-Dx model for diagnosing CAV achieved excellent discrimination, with an AUROC of 0.91, whereas the HistoCAV-Pr model for predicting CAV achieved good performance with an AUROC of 0.80. The integrated iCAV-Pr model achieved excellent predictive performance, with an AUROC of 0.93 on the held-out test set.

Conclusions:

Prediction of future CAV development is greatly improved by incorporation of computationally extracted histological features. These results suggest morphological details contained within regularly obtained biopsy tissue have the potential to enhance precision and personalization of treatment plans for patients after heart transplant.
Post-collection acidification of spot urine sample is not needed before measurement of electrolytes
Authors: Šálek Tomáš , Musil Pavel , Pšenčík Marek , Palička Vladimír
Published: April 2022

Kidney stone formers can have higher oxalate and phosphate salt amounts in their urine than healthy people and we hypothesized that its acidification may be useful. The study aims to compare results of urine concentrations of calcium, magnesium, and inorganic phosphorus in the midstream portion of first voided morning urine samples without (FMU) and with post-collection acidification (FMUa) in kidney stone patients.
This is a prospective single center study. A total of 138 kidney stone patients with spot urine samples were included in the study. Urine concentrations of calcium, magnesium and inorganic phosphorus were measured with and without post-collection acidification. Acidification was performed by adding 5 µL of 6 mol/L HCl to 1 mL of urine.
The median age (range) of all participants was 56 (18-87) years. The median paired differences between FMU and FMUa concentrations of calcium, magnesium, and inorganic phosphorus were: - 0.040 mmol/L, 0.035 mmol/L, and 0.060 mmol/L, respectively. They were statistically different: P < 0.001, P < 0.001, P = 0.004, respectively. These differences are not clinically significant because biological variations of these markers are much higher.
No clinically significant differences in urinary calcium, magnesium, and inorganic phosphorus concentrations between FMU and FMUa in patients with kidney stones were found.
Long pentraxin 3 as a marker of COVID-19 severity
Authors: Canetta Ciro , Assandri Roberto , Serana Federico , Tolassi Chiara , Scartabellati Alessandro , Buscarini Elisabetta , Accordino Silvia
Published: April 2022

Several laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters.
Stored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay.
A total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P < 0.001). Univariate and multivariate logistic regression models demonstrated that the only significant laboratory predictor of ICU stay was PTX3 (OR: 1.68 (1.19-2.29), P = 0.003), after controlling for comorbidities. The Receiver Operator Characteristic curve analysis showed that PTX3 had a higher accuracy compared to C-reactive protein (CRP), lactate dehydrogenase (LD), ferritin in identifying ICU patients (AUC of PTX3 = 0.98; CRP = 0.66; LD = 0.70; ferritin = 0.67, P < 0.001). A cut-off of PTX3 > 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU.
High values of PTX3 predict a more severe COVID-19.
A Polynesian, a Jew, and a Hindu Walk into Jerusalem: On Mendelssohn’s Religious Universalism
Authors: Fogel Jeremy
Published: April 2022

In his Jerusalem, Moses Mendelssohn describes a Polynesian visitor to Dessau before traveling to India by way of ancient Jerusalem. In two pages, Mendelssohn has crossed the world, doing so to argue that in spite of their cultural differences, most human beings ultimately share basic salvific religious truths. This paper explores the religious universalism reflected in this striking passage, analyzes Mendelssohn’s cultural sensitivity and pluralism, and offers a characterization of the particularities of Mendelssohn’s Jewish universalism as well as concluding thoughts on the varieties of universalism more generally.
The Servant-Queen
Authors: Pass Bruce
Published: April 2022

This article outlines Bavinck’s conceptualization of theology as the servant-queen of the sciences. The potential contribution Bavinck makes to the contemporary debate over the place of theology in the university is considered, paying attention to the historical context in which it was framed, recent objections to any revival of the claim that theology is the queen of the sciences, and a notable lacuna in Bavinck’s reflections on this subject.
“To Tend Directly Toward God”
Authors: Reed Ryan
Published: April 2022

The aim of this article is to consider John Calvin’s thinking on humanity’s telos. In it, I argue that Calvin embraces the structure of eudaimonistic anthropology that human life is ordered to an all-encompassing telos, though he significantly modifies the content of this framework in line with his Christian commitments, holding that humanity needs grace to reach its final end and that the final end is bound up with eternal life and God. To show this aspect of his thought, I consider three elements of his anthropology. First, I note how Calvin thinks of human nature as incomplete and having innate potentialities to be realized. Second, I observe the role that rationality plays in achieving this telos both before and after the Fall. Finally, I conclude by discussing Calvin’s specific understanding of the nature of humanity’s telos.
On the Non-enforceability of the Penal Sanctions in the Mosaic Law
Authors: Flowers Michael V.
Published: April 2022

Although the “theonomy” debate has largely subsided, it continues to be espoused by a vocal minority because it was never properly addressed. The key issue is not whether the judicial laws are still binding. These laws are grounded in God’s moral character; hence, they are still binding. But since they were enforced by magistrates who worked in conjunction with Levitical priests in the context of a now-defunct priesthood, today’s magistrates would lack the divine guidance and authority to enforce the judicial laws as was once prescribed. A conceptual distinction should therefore be drawn between moral/judicial laws and their legal enforcement in society.
10. Bangsamoro
Authors: Riordan S.J. Patrick
Published: April 2022

Patrick Riordan proposes in this chapter a case study of Bangsamoro (a new autonomous region in the southern Philippines) from the perspective of common good dynamics. The common quest for autonomy must accommodate a complex reality in Bangsamoro with an indigenous population composed of Muslim and Animist and the new, usually Christian settlers. This case study analyses the building of the complex equilibrium of common goods from the perspective of the five key drivers identified in the matrix. It shows that the quest for autonomy can be seen as the creation of a nexus of common good, with the matrix highlighting political and social strategic priorities in this process.