bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic roles and therapeutic potential of the CCL8–CCR8 axis in a murine model of IgG4-related sialadenitis
Authors: Honda Fumika , Tsuboi Hiroto , Ono Yuko , Abe Saori , Takahashi Hiroyuki , Ito Kiyoaki , Yamada Kazunori , Kawano Mitsuhiro , Kondo Yuya , Asano Kenichi , Tanaka Masato , Malissen Marie , Malissen Bernard , Matsumoto Isao , Sumida Takayuki
Published: April 2021

Background Our previous studies reveal that CCL18-CCR8 chemokine axis is upregulated in patients of immunoglobulin G4-related disease (IgG4-RD), suggest that the CCL18–CCR8 axis is implicated in the etiology of IgG4-RD. Although, whether this axis has a potential as a therapeutic target remains unclear. Our purpose was to clarify the pathogenic roles and therapeutic potential of the murine CCL8 (analogue of human CCL18)–CCR8 axis by using an animal model of IgG4-RD (LAT Y136F knockin mice; LAT mice).Methods We compared the infiltration of inflammatory cells and the fibrosis of the salivary glands of 6-week-old LAT mice and littermate mice. The expressions of Ccl8 and Ccr8 were also compared. Next, we investigated the therapeutic effects of intravenous administration of anti-CCL8 neutralizing antibody in LAT mice against inflammation and fibrosis of the salivary glands. We also investigated the effects of stimulation with recombinant mouse CCL8 on the collagen production in a mouse fibroblast cell line (NIH/3T3) in vitro.Results When compared with the littermates, the LAT mice showed apparent infiltration of inflammatory cells, and fibrosis in the salivary glands. The focus and fibrosis score in the salivary glands were significantly higher in the LAT mice than in the littermates. The expression levels of Ccl8 in the spleen and of Ccr8 in the salivary glands were significantly higher in the LAT mice than in the littermates. Anti-CCL8 antibody significantly improved the focus and fibrosis score in the salivary glands of the LAT mice. In vitro, stimulation with recombinant mouse CCL8 significantly increased the expression of collagen and ERK1/2 phosphorylation in NIH/3T3.Conclusion We clarified the overexpression and therapeutic potential of the mouse CCL8–CCR8 axis in LAT mice, which could play a crucial role in fibrosis via ERK1/2 phosphorylation, as well as the chemotaxis of inflammatory cells. The human CCL18–CCR8 axis might be a novel therapeutic target for IgG4-RD.
Modeling and Forecasting of Sunspots Cycles: An Application of ARMA (p, q)-GARCH (1, 1) Model
Authors: Zaffar Asma
Published: April 2021

The influence of the earth climatic condition of oscillations of solar activity is measurable only in the long run duration. Modeling of the sunspots is an initial role for the mankind utilization of the benefits because solar activity has influenced on the earth’s climates. Time series analysis and modeling have proved to stick out amidst with other statistical tools when estimating and predicting solar activities. This study emphasis on the appropriateness of the generalized autoregressive conditional heteroskedasticity (GARCH) models with specification autoregressive ARMA (p, q) process in terms of their performance for delivering volatility forecasts for Sunspot cycles. In this study, individual sunspots cycle’s ranging from cycle 1st to 24th (1755–2019) are considered. To notice the appropriateness of Autoregressive Conditional Heteroscedastic (ARCH) effect on sunspot cycles data, Lagrange Multiplier test is used. ARMA (p, q)-GARCH (1, 1) process expresses leptokurtic that is fat and heavy tail (values are strongly correlated to each other). The sunspot cycles ARMA (p, q)-GRACH (1, 1) process expresses the positive skewness except cycles 4th and 19th. Most of the Sunspot cycles (1st, 4th, 12th, 13th, 14th, 15th, 16th, 19th, 20th, 23rd and 24th ) follow Auto-Regressive and moving Average (ARMA (2, 2))-GARCH (1, 1). Sunspot cycles (5th, 6th, 7th and 15th ) follow ARMA (3, 3)-GARCH model. Whereas the cycles (2nd and 11th ) show appropriate model is ARMA (5, 1) -GARCH (1, 1) process. ARMA (5, 3) -GARCH (1, 1) process expresses cycles (18th and 19th ). The ARMA (2, 2)-GARCH (1, 1) stationary volatility model expresses the finest forecasting model as compared with other models. Though, ARMA (2, 2)-GARCH (1, 1) is the adequate model for estimation and forecasting most of the sunspot cycles. The results that are obtained by this study are very beneficial for observing the influence of solar activity on the earth's climate.
An experimental approach to evaluate the role of rock failure modes in mechanical characterization of metabasalts
Authors: Bhowmick Sreyashi , Ram Bikash Kumar , Mondal Tridib Kumar
Published: April 2021

A detailed understanding on rock failure modes testifies the competence of support designs for engineering work. Studying such failure modes using physical models of rock samples under laboratory conditions can be time efficient, informative and economically viable. In this study, the mechanical behavior of massive metabasalts were characterized with reference to rock failure modes through index tests such as point load and Brazilian testing conditions. Rock failure modes under point load test are categorized as i) single plane failure mode, ii) triple junction failure mode, iii) twisted failure mode and iv) single plane (inclined). It is observed that twisted and triple junction failure modes are observed for the samples with higher point load strength values (> 6 MPa). A total of five types of rock failure modes were observed in metabasalts under Brazilian testing conditions such as i) central multiple, ii) central, iii) non-central, iv) central multiple + layer activation and v) conjugate failure modes. Central multiple failure mode is found to be the most common failure mode in metabasalts due to its massive nature. It is also observed that all failure modes under Brazilian test are transpired in the range of 8 to 12 MPa. Among all other perceived rock failure modes, single plane (inclined) and conjugate failure modes under point load and Brazilian tests respectively are introduced in this study. It is evident that rock failure modes, which lead to control the strength of the rocks, should be considered as an important aspect for mechanical characterization of rock materials.
Histology and Clinical Characteristics of Asymptomatic Treatment-naïve Children with Chronic Hepatitis B in Shanghai China
Authors: Hu Yao , Wu Xia , Ye Yingzi , Ye Lijing , Han Shuzhen , Zhu Qirong , Wang Xiaohong , Yu Hui
Published: April 2021

BACKGROUND & AIMS: Chronic hepatitis B (CHB) virus infection is a major cause of morbidity and mortality. We aim to investigate the association between hepatic histology and clinical characteristics in asymptomatic treatment-naïve children chronically infected with hepatitis B virus (HBV) in Shanghai China. METHODS: Liver biopsies of 278 asymptomatic treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation and fibrosis, and correlated with clinical and laboratory data. RESULTS: The clinical, virologic and pathologic features of chronic HBV infection were studied in 278 treatment-naïve children from Shanghai, China, of who were all asymptomatic. And 177 (63.7%) of the children were male. Sera from mothers of 277 of these children were HBsAg positive. Up to 87.4% of subjects were hepatitis B e antigen-positive at the time of the biopsy. The median age at biopsy was 5.1 years (interquartile range 2.8-8.4 years). HBV DNA levels were generally high (mean 7.4 log10 IU/mL), as was serum alanine aminotransferase (median 105 U/L). Using the Ishak-modified histology activity index scoring system, no inflammation was seen in 2.9% cases, mild inflammation was in 22.3%, moderate in 73.4%, and severe in 1.4%. No fibrosis was seen in 11.5%, mild fibrosis in 32.7%, moderate fibrosis in 47.5%, and cirrhosis in 8.3%. When serum ALT level was < 80 (2×ULN) and > 80 U/L, the degree of inflammation (P<0.0001) and fibrosis stage (P<0.0001) had significant differences. Inflammation and fibrosis aggravated with ALT level increasing. Fibrosis stage had significant differences between age of <3 and >3 years (P<0.0001). Moderate fibrosis and cirrhosis rate was relatively higher in children aged <3 years at biopsy. No correlation was found between histological changes with gender, HBV genotypes or HBV DNA levels. CONCLUSION: Significantly wide range of inflammation and fibrosis is seen in asymptomatic treatment-naïve children with chronic hepatitis B in Shanghai China. Serum ALT >80 U/L may be a strong indicator of the degree of hepatic inflammation and severity of fibrosis. Moderate fibrosis and cirrhosis has already appeared in aged <3 years children.
A 40-year Evaluation of Drivers of African Rainforest Change
Authors: Chapman Colin , Galán-Acedo Carmen , Gogarten Jan F. , Hou Rong , Lawes Michael J. , Omeja Patrick A. , Sarkar Dipto , Sugiyama Anna , Kalbitzer Urs
Published: April 2021

Background: Tropical forests are repositories of much of the world’s biodiversity and are critical for mitigation of climate change. Yet, the drivers of forest dynamics are poorly understood. This is in large part due to the lack of longitudinal data on forest change and changes in drivers.Methodology: We quantify changes in tree abundance, diversity, and stand structure along transects first enumerated in 1978 and resampled 2019 in Kibale National Park, Uganda. We tested five predictions. First, based on the purported role of seed dispersal and herbivory and our quantification of changes in the abundance of frugivores and herbivores, we tested two predictions of how faunal change could have influenced forest composition. Second, based on an evaluation of life history strategies, we tested two predictions concerning how the forest could have changed following disturbance that happened prior to written history. Finally, based on a 50-year climate record, we test the possible influence of climate change on forest dynamics. Results: More trees were present on the assessed transects in 2019 (508) than in 1978 (436), species richness remained similar, but diversity declined as the number of dominant species increased. Rainfall increased by only 3 mm over the 50 years but this effect was not significant. Annual average monthly maximum temperature increased significantly by 2.2°C over 50 years. The abundance of frugivorous and folivorous primates and elephants increased over the 50 years of monitoring. The predictions that as the abundance of seed dispersing frugivores increases the abundance of their preferred fruiting tree species would increases and that as the abundance of folivorous would cause a decline in their preferred species were both not supported. Since Kibale was disturbed prior to historical records, we predicted that light-demanding species would decrease in abundance, while shade-tolerant species would increase - this was supported. Finally, while temperature increased over the 50 years, we found no means to predict a priori how individual species would respond.Conclusions: Our study revealed subtle changes in the tree community over 40 years, sizable increases in primate numbers, a substantial increase in the elephant population and an increase in local temperature. Yet, a clear picture of what set of interactions impact the change in the tree community remains elusive. Our data on tree life-history strategies and frugivore/herbivore foraging preferences suggest that trees species are under opposing pressures.
Identification of MAP3K15 as a Potential Prognostic Biomarker and Correlation with Immune Infiltrates in Osteosarcoma
Authors: Chen Zhuning , Kong Haoran , Cai Zhaopeng , Chen Keng , Wu Boyang , Li Haonan , Wang Peng , Wu Yanfeng , Shen Huiyong
Published: April 2021

Background: Osteosarcoma (OS) is a type of primary malignant tumor, and increasing amounts of evidence show the clinical benefits of immunotherapy in treating OS. However, the lack of comprehensive studies on the complex OS immune microenvironment hinders the application of immunotherapy. Thus, we aimed to systematically study the immune characteristics of OS and identify novel biomarkers for OS treatment.Methods: We systematically studied the immune score and proportion of infiltrating immune cells in OS in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases using the ESTIMATE and CIBERSORT algorithms. Differential expression and functional analyses were used to identify dysregulated genes and explore their functions. Survival and Cox regression analyses were applied to establish an immune-related prognostic signature. The expression of MAP3K15 was performed by qPCR assay and immunohistochemistry. We divided 48 patients into high expression and low expression groups according to MAP3K15 expression.Results: A total of 103 differentially expressed immune genes (DEIGs) were found in the TARGET-OS and GSE39058 databases, and these DEIGs were mainly enriched in leukocyte proliferation, leukocyte differentiation, osteoclast differentiation, natural killer (NK) cell-mediated cytotoxicity and the adaptive immune system. A predictive signature was constructed based on the survival analysis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.65. Moreover, we found that mitogen-activated protein kinase kinase kinase 15 (MAP3K15) can predict the prognosis of patients with OS and is closely related to CD4 T cells, M0 macrophages, and M1 macrophages. We found that patients with high MAP3K15 expression had a significantly poorer prognosis Conclusions: Our study found that MAP3K15, whose expression level is closely related to immune activity in tumors, was a critical immune-related biomarker and may provide a basis for OS immunotherapy. Clinical Trial RegistrationNot applicable.
Pharmaceuticals and Personal Care Products (PPCPs) Impact Enriched Nitrifying Cultures
Authors: Lopez Carla , Nnorom Mac-Anthony , Tsang Yiu Fai , Knapp Charles W
Published: April 2021

The impact of pharmaceutical and personal care products (PPCPs) on the performance of biological wastewater treatment plants (WWTPs) has been widely studied using whole-community approaches. These contaminants affect the capacity of microbial communities to transform nutrients; however, most have neither honed their examination on the nitrifying communities directly nor considered the impact on individual populations. In this study, six PPCPs commonly found in WWTPs, including a stimulant (caffeine), an antimicrobial agent (triclosan), an insect repellent ingredient (N,N-diethyl-m-toluamide (DEET)), and antibiotics (ampicillin, colistin, and ofloxacin), were selected to assess their short-term toxic effect on enriched nitrifying cultures: Nitrosomonas sp. and Nitrobacter sp. The results showed that triclosan exhibited the greatest inhibition on nitrification with EC50 of 89.1 µg L− 1. From the selected antibiotics, colistin significantly affected the overall nitrification with the lowest EC50 of 1 mg L− 1, and a more pronounced inhibitory effect on ammonia-oxidizing bacteria (AOB) compared to nitrite-oxidizing bacteria (NOB). The EC50 of ampicillin and ofloxacin were 22 and 12.7 mg L− 1, respectively. Additionally, experimental data suggested that nitrifying bacteria were insensitive to the presence of caffeine. In the case of DEET, moderate inhibition of nitrification (< 40%) was observed at the highest concentration tested. These findings contribute to the understanding of the response of nitrifying communities in presence of PPCPs, which play an essential role in biological nitrification in WWTPs. Knowing specific community responses helps develop mitigation measures to improve system resilience.
The Use of Kumpfer's Resilience Framework in Understanding the Breastfeeding Experience of Employed Mothers After Returning to Work: a Qualitative Study in China
Authors: Guo Hong Hua , Zhou Rong , Li Min Xiang , Zhang Si Qi , Yi Huan Ying , Wang Lin Jie , Li Tong , Zhang Cai Hong , Lu Hong
Published: April 2021

Background: The increasing numbers of women in the workforce is an inevitable trend in China. More and more employed women stop breastfeeding because of working stressors. However, there are also many mothers overcoming many challenges to insist on breastfeeding after returning to work. Their individual experience of breastfeeding may provide a new insight to promote and support breastfeeding on employed mothers. This study sought to understand mothers’ experience with insisting on breastfeeding after returning to work based on Kumpfer’s Resilience Framework in Chinese context. Methods: This qualitative study was designed with semi-structured interviews. Purposive sampling and snowball sampling was employed to recruit 13 full-time working mothers with a stable job in the public sector who continued to breastfeed for 1 month or more after returning to work in Haikou, Hainan Province, China. Interviews were conducted from January to March 2020 to capture participants’ experiences of breastfeed after returning to work. Grounded theory and Kumpfer’s Resilience Framework were used to analyze data via a systematic and iterative process.Results: Employed mothers built resilience while continuing to breastfeed after returning to work. The core concept was "dynamic interaction". Other categories were the background and explanation of this phenomenon. For working mothers who continued to breastfeed, resilience involved "dynamic interaction", which started from "experiencing stressors" and "obtaining support", two factors that interacted with the individual to "stimulate resilience", which led to “behavioral resilience” during the ongoing dynamic interaction between resilience and environmental factors and ultimately led to three different "weaning outcomes", including natural weaning, active weaning, and forced weaning. Conclusions: This study identified the framework of resilience in mothers who insisted on breastfeeding after returning to work based on Kumpfer’s Resilience Framework. It may help midwives assess stressors and supports for employed mothers to continue to breastfeed after returning to work, determine the process by which resilience traits are stimulated in employed mothers, identify different phases of behavioral resilience, provide targeted interventions, and then promote favorable weaning outcomes.
Identification of Metabolomic Biomarkers of Seed Vigor and Aging in Hybrid Rice
Authors: Chen Bingxian , Gao Jiadong , Yan Shijuan , Zhang Yinxin , Zhang Qi , Fu Hua , Liu Jun
Published: April 2021

BackgroundSeed deterioration during rice seed storage will lead to seed vigor loss, which adversely affects agricultural production, the long-term preservation of germplasm resources, and the conservation of species diversity. However, the mechanisms underlying seed vigor maintenance remain largely unknown. ResultsIn this study, 16 hybrid rice combinations were selected from four sterile lines and four restorer lines. Following artificial aging and natural aging treatments, the metabolite markers that could accurately reflect the aging degree of the hybrid rice seeds were identified based on the germination percentage and metabolomics analysis by gas chromatography-mass spectrometry. Significantly differences in the degree of seed deterioration were observed among the 16 hybrid rice combinations tested, with each restorer and sterile lines after storage having the different germination percentage. The hybrid rice combination with the storage-resistant restorer line Guanghui122 exhibited the highest germination percentage under both natural and artificial storage. A total of 89 metabolic peaks and 56 metabolites were identified, most of which were related to primary metabolism. Interestingly, the content of galactose, gluconic acid, fructose and glycerol in the seeds increased significantly during the aging process. Absolute quantification indicated that galactose and gluconic acid were very significantly negatively correlated with the germination percentage of the seeds under the different aging treatments. The galactose content was significantly positively correlated with gluconic acid content. Additionally, while the relative content of raffinose did not change much during storage, a significant positive correlation between raffinose and the germination rate of the artificially aged seeds before storage was detected.ConclusionBased on the metabolomics, metabolite markers which could accurately reflect the aging degree of hybrid rice seeds were identified. Galactose and gluconic acid were very significantly negatively correlated with the germination percentage of the seeds which suggested that these metabolites could constitute potential metabolic markers of seed aging. These findings are of great significance for the rapid and accurate evaluation of seed aging, the determination of seed quality, and the development of molecular breeding approaches for high-vigor rice seeds.
Predictors And Reasons of Inappropriate Hospitalizations For Surgical Patients in A Tertiary Hospital in Wuhan, China: A Retrospective Study
Authors: Li Hao , Tao Hongbing , Li Gang
Published: April 2021

Background The first step in every quality improvement process is the identification the problem and its extent. We aim to analyze the frequency and its associated factors of inappropriate hospitalization for a tertiary hospital in Wuhan and ascertain the specific reasons for each IHDs to provide evidence for further reduction of inappropriate hospital days.Results A total of 4586 days of hospital stay from 408 cases were evaluated by A cross-sectional and retrospective audit program carried out in a third-level teaching hospital with 5613 beds and 9623 faculty in Wuhan, China. 320 cases (78.43%) were reported to have experience at least one IHD and 1053 hospital days (23.31%) were found to be inappropriate. Predictors of higher levels of inappropriateness with surgery were patients at the age of 60-69(OR=2.328, 95% CI=1.359-3.989) before the surgery, and use of ventilators(OR=2.127, 95%CI=1.116-2.839), admission from outpatient(OR=5.724, 95%CI=1.579-20.744), multiple diagnosis(OR=1.604, 95%CI=1.059-2.432), and higher surgical incision level(OR=2.152, 95%CI=1.391-3.327) after surgery. The main causes of inappropriateness were medical factors that were related to the healthcare services providers, however, the patient factors gave rise to nearly a quarter of IHDs after surgery.Conclusions The prevalence of IHDs was 23.31% in this tertiary hospital in Wuhan. Findings from this study indicate that the characteristics of surgical patients from different phases(preoperative/postoperative) are supposed to be taken into account to develop efficient and feasible interventions for IHD reduction.
What is the current clinical practise in pituitary adenoma surgery in Europe? European Pituitary Adenoma Surgery Survey (EU-PASS) results - technical part
Authors: Májovský Martin , Grotenhuis Andre , Foroglou Nicolas , Zenga Francesco , Froehlich Sebastien , Ringel Florian , Sampron Nicolas , Thomas Nick , Komarc Martin , Netuka David
Published: April 2021

Pituitary adenoma surgery has evolved rapidly in recent decades, changing clinical practice markedly and raising new challenges. There is no current consensus or guidelines for perioperative care that includes possible complication management. This study aims to determine current practice across European neurosurgical centers. We created a list of eligible departments performing pituitary adenoma surgery based on cooperation with EANS, Νational neurosurgical societies, and personal communication with local neurosurgeons. We contacted the chairpersons from each department and asked them (or another responsible neurosurgeon) to fill out the survey. The survey consisted of 58 questions. For further analysis, departments were divided into subgroups: “academic”/”non-academic center”, “high-volume”/”low-volume”, “mainly endoscopic”/“mainly microscopic”/“mixed practise” and by geographical regions. Data from 254 departments from 34 countries were obtained. The average time to complete the survey was 18 min. Notably, the endoscopic approach is the predominant surgical approach in Europe, used in 56.8% of the centers. In routine cases without intraoperative cerebrospinal fluid leak, high-volume centres are less pedantic with sellar closure when compared with low-volume centres. On the other hand, when a postoperative cerebrospinal fluid leak occurs, high-volume centres are more active and indicate early reoperation. Less than 15% of the participating centres perform early postoperative MRI scans. Marked variation was noted among different groups of respondents and some contentious issues are discussed. Such information can encourage useful debate about the reasons for the variations seen and perhaps help develop standardised protocols to improve patient outcomes. A future research focus is to compare European results with other regions.
Risk of primary lung cancer after breast cancer radiotherapy: A systematic review and meta-analysis
Authors: Zareie Bushra , Rasouli Mohammad Aziz , Poorolajal Jalal
Published: April 2021

Background: Epidemiological studies have shown that the risk of secondary malignancies may increase by radiotherapy. Lung cancer is the most important long-term complication of breast cancer radiotherapy.Methods: Major electronic databases including Scopus, Web of Science, and MEDLINE were searched. All cohort studies that investigated the association between radiotherapy for breast cancer and risk of primary lung, bronchus and trachea cancers conducted until March 2021 were included. The study participants were evaluated regardless of their age and ethnicity. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The designated effects were risk ratio (RR). The random-effects model was used to estimate the average effects.Results: Fifteen studies including 1,640,247 women with primary breast cancer were identified of which 937,151 had not received radiotherapy and 703,096 subjects had received radiotherapy. In general, there was no significant association between breast cancer radiotherapy and lung cancer based on 10 studies (RR=0.95, 95%CI: 0.87-1.02, P=0.15), There was no association between breast cancer radiotherapy and lung, bronchus, and trachea cancers either based on 5 studies (RR=0.98, 95%CI: 0.93-1.02, P=0.32).Conclusion: Radiotherapy for breast cancer is not associated with an excess risk of lung cancer. Due to the limited number of studies, further research about lung doses from breast cancer radiotherapy varied substantially worldwide, is suggested to the risk of lung cancer after breast cancer radiotherapy.
Pseudoboehmite as a drug delivery system for acyclovir
Authors: Peres Renato Meneghetti , Sousa Jéssica Maiara Leme , de Oliveira Mariana Oliva , Rossi Maura Vincenza , de Oliveira Rene Ramos , de Lima Nelson Batista , Bernussi Ayrton , Warzywoda Juliusz , Sarmento Bruno , Munhoz Antonio H.
Published: April 2021

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of low permeability across the gastrointestinal membrane. Based on experiments using nanoparticles of pseudoboehmite as a drug delivery system in vitro assays it was concluded that pseudoboehmite could be used for acyclovir release. We report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles. Pseudoboehmite was characterized by several techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content in the plasma of Wistar rats after 4 h administration. The toxicity of pseudoboehmite was also evaluated using the Caco-2 cell line (ATCC).
Procyanidin C1 is a natural agent with senolytic activity against aging and age-related diseases
Authors: Xu Qixia , Fu Qiang , Li Zi , Liu Hanxin , Wang Ying , Lin Xu , He Ruikun , Zhang Xuguang , Campisi Judith , Kirkland James , Sun Yu
Published: April 2021

Aging causes functional decline of multiple organs and increases the risk of age-related pathologies. In advanced lives, accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP), promotes chronic inflammation and causes diverse conditions. Here we report the frontline outcome of screening a natural product library with human primary stromal cells as an experimental model. Multiple candidate compounds were assayed, and grape seed extract (GSE) was selected for further investigation due to its leading capacity in targeting senescent cells. We found procyanidin C1 (PCC1), a polyphenolic component, plays a critical role in mediating the antiaging effects of GSE. PCC1 blocks the SASP expression when used at low concentrations. Importantly, it selectively kills senescent cells upon application at higher concentrations, mainly by enhancing production of reactive oxygen species (ROS) and disturbing mitochondrial membrane potential, processes accompanied by upregulation of Bcl-2 family pro-apoptotic factors Puma and Noxa in senescent cells. PCC1 depletes senescent cells in treatment-damaged tumor microenvironment (TME) and enhances therapeutic efficacy when combined with chemotherapy in preclinical assays. Intermittent administration of PCC1 to both senescent cell-implanted mice and naturally aged animals alleviated physical dysfunction and prolonged post-treatment survival, thus providing substantial benefits in late life stage. Together, our study identifies PCC1 as a distinct natural senolytic agent, which may be exploited to delay aging and control age-related pathologies in future medicine.
Assessment of Cardiac Functions and Subclinical Cardiovascular Risk In Children with Urolithiasis: An Initial Study
Authors: Elmacı Ahmet Midhat , Alp Hayrullah , Dönmez Muhammet İrfan
Published: April 2021

Information on cardiovascular problems related to childhood urinary stone disease is limited. The aim of this study is to assess the ventricular functions and subclinical cardiovascular risk in children with urolithiasis using echocardiographic measurements. Children readily diagnosed with urolithiasis were enrolled in the study as well as children with no urinary stone disease confirmed via urinary ultrasonography. Body mass index (BMI) and blood pressures were noted as well as basic serum parameters. Carotid intima media thickness (cIMT), epicardial fat tissue (EFT) thickness and periaortic fat tissue (PFT) thickness were measured via transthoracic echocardiography in addition to pulsed and tissue Doppler imaging. Myocardial performance indexes were also calculated and correlation analyses were made. A total of 17 patients (10 boys) were enrolled in the study with a mean age of 8.57 ± 2.62 years. There were 17 children (12 boys) in the control group and their mean age was 9.53 ± 1.72 years. There was no statistically significant difference between the two groups in terms of demographic and laboratory variables. Tissue Doppler echocardiography revealed that Tei indexes of left ventricle, right ventricle and septum were significantly higher in the study group than in the controls (p < 0.001 for all). The cIMT (0.041 ± 0.012 vs. 0.025 ± 0.002), EFT (0.432 ± 0.083 vs. 0.325 ± 0.032) and PFT thicknesses (0.138 ± 0.029 vs. 0.113 ± 0.008) of the study group were statistically higher than the control group (p < 0.001, p < 0.001 and p = 0.002, respectively) indicating a higher CVD risk.Conclusions: Children with urolithiasis presented not only biventricular early systolic and diastolic dysfunction but also subclinical atherosclerosis in early ages. Cardiovascular complications should be considered in the follow-up and treatment of these patients.
Development of a novel multifocal lens using a polarization directed flat lens: Possible candidate for a multifocal intraocular lens
Authors: Na Kyung-Sun , Lee Chang Su , Kim Da Ran , Cho Soo Yeon , Kim Eun Chul , Kim Hyun Seung , Hwang Ho Sik
Published: April 2021

Background: A polarization-directed flat (PDF) lens acts as a converging lens with a focal length (f) > 0 and a diverging lens with f < 0, depending on the polarization state of the incidental light. To produce a multifocal lens with two focal lengths, a PDF and a converging lens having shorter focal length were combined. In this study, we tested to determine its potential as a new multifocal intraocular lens (IOL).Methods: Constructed a multifocal lens with a PDF lens (f=+/- 100 mm) and a converging lens (f= +50 mm). In an optical bench test, we measured the lens’s focal lengths to test the multifocal function. The multifocal function and optical quality of the lens in various situations were tested. An Early Treatment Diabetic Retinopathy Study (ETDRS) chart as a near target and a parking lot as a distant target were photographed using a digital single-lens reflex (DSLR) camera. Both lenses (multifocal and monofocal) were tested under same conditions. Results: In the optical bench test, the multifocal lens’s focal lengths were 31.2 and 71.2 mm. In the DSLR test using the multifocal lens, the parking lot appeared slightly cloudy compared to the monofocal lens results. With the multifocal lens, the ETDRS chart’s images became blurry as the ETDRS chart’s distance decreased, but became very clear again at a certain position.Conclusions: We confirmed the multifocal function of the multifocal lens using a PDF lens. This lens can be used as a multifocal IOL in the future.
Treatment and Survival Analysis for 40-year SEER Data on Upper Esophageal Cancer
Authors: Zhu Ming-Chuang , Li Guoliang , Xiong Peng , Zhu Min
Published: April 2021

Background: Upper esophageal cancer (UEC) is rare in western countries. We elucidated the survival outcomes of UEC and analyzed factors associated with prognosis of UEC using the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rate were calculated by Kaplan–Meier method. Cox proportional hazard regression was used to analyze predictive factors.Results: Since 1973, there has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p<0.001) and median ECSS (7 months vs. 11months, p < 0.001) among patients with UEC. The ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). For patients with localized disease, ECSS and OS were highest among patients treated with SWR, compared with patients with R+S and RWS. For patients with regional disease, ECSS and OS were highest among patients with R+S, compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy, compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC.Conclusion: Although survival of patients with UEC has gradually increased since 1973, the long-term survival among this patient population remains poor. Effective treatments for UEC include surgery, radiotherapy, and combination of surgery and radiotherapy.
Analyses of Predictive Factors Associated with Hypocalcemia and Elevated iPTH with Normocalcemia after Ultrasound-guided Radiofrequency Ablation for Primary Hyperparathyroidism
Authors: Chai Hui-Hui , Zhao Yu , Ye Rui-Zhong , Zeng Zeng , Zhang Zheng-Xian , Hu Qiao-Hong , Pang Hai-Su , Peng Cheng-Zhong
Published: April 2021

Purpose

To assess the feasibility of ultrasound-guided (US-guided) radiofrequency ablation (RFA) for primary hyperparathyroidism (PHPT) and determine predictive factors for hypocalcemia and elevated serum intact parathyroid hormone(ePTH) with normocalcemia after ablation.
Materials and Methods

Between January 2015 and January 2021, data from 44 patients with PHPT who were treated with US-guided RFA were retrospectively evaluated. Serum intact parathyroid hormone(iPTH), total calcium (Ca), phosphorus, alkaline phosphatase (ALP), and 25-hydroxyvitamin D3 (25(OH)D3) levels and the volume of the abnormal enlarged parathyroid glands were recorded before RFA. Changes in iPTH and Ca levels at 1 and 3 days, and, 1, 3, and 6 months after ablation were recorded.
Results

Overall, thirteen patients developed hypocalcemia 1–3 days after RFA. ePTH with normocalcemia developed in 17 patients 1 month after RFA. Thirty-two patients were followed up for more than 6 months, and 27 of these patients had sustained normalized values for both serum iPTH and Ca levels more than 6 months after RFA. There were significantly more patients who developed hypocalcaemia, when the baseline ALP was greater than 261.5 U/L (sensitivity 61.5%, specificity 100.0%). The risk of ePTH decreased by 21.7% for every 1 ng/mL increase in 25 (OH) D3. The risk of ePTH was increased when a patient's serum iPTH was higher than 172.4 pg/mL (sensitivity 88.2%, specificity 76.2%).
Conclusions

US-guided RFA is feasible for clinical management of PHPT patients. Hypocalcaemia following RFA was associated with higher pre-RFA serum ALP levels. Elevated iPTH levels with normocalcemia at 1 month after RFA were associated with pre-RFA vitamin D deficiency and higher baseline iPTH levels. Patients with higher serum ALP and iPTH and lower 25 (OH) D3 levels before RFA need to be managed carefully and monitored closely after RFA of PHPT.
Melatonin reduces neuroinflammation and improves axonal hypomyelination by modulating M1/M2 microglia polarization via JAK2-STAT3-telomerase pathway in postnatal rats exposed to lipopolysaccharide
Authors: Zhou Qiuping , Lin Lanfen , Li Haiyan , Jiang Shuqi , Wang Huifang , Huang Peixian , Lin Qiongyu , Chen Xuan , Deng Yiyu
Published: April 2021

Microglia activation and associated inflammation are implicated in the periventricular white matter damage (PWMD) in septic postnatal rats. This study investigated whether melatonin would mitigate inflammation and alleviate the axonal hypomyelination in the corpus callosum in septic postnatal rats. We further explored if this might be through modulating microglial polarization from M1 phenotype to M2 through JAK2/STAT3/telomerase pathway. We reported here that melatonin, indeed, not only can it reduce the neurobehavioral disturbances in LPS injected rats, but it can also dampen microglia mediated inflammation. Thus, in LPS + melatonin group, expression of proinflammatory mediators in M1 phenotype microglia was downregulated. As opposed to this, M2 microglia were increased which was accompanied by upregulated expression of anti-inflammatory mediators along with TERT or MT1. In parallel to this was decreased NG2 expression but increased expression of myelin and neurofilament proteins. That melatonin can improve hypomyelination was confirmed by electron microscopy. In vitro in primary microglia stimulated by LPS, melatonin decreased the expression of proinflammatory mediators significantly; but it increased expression of anti-inflammatory mediators. Additionally, the expression levels of p-JAK2 and p-STAT3 were significantly elevated in microglia after melatonin treatment. Remarkably, the melatonin effects on LPS treated microglia was blocked by melatonin receptor, JAK2, STAT3 and telomerase reverse transcriptase inhibitors, respectively. Taken together, it is concluded that melatonin can attenuate PWMD through shifting M1 microglia towards M2 via MT1/JAK2/STAT3/telomerase pathway. The results suggest a new therapeutic strategy whereby melatonin may be adopted to convert microglial polarization that would ultimately contribute to attenuation of PWMD.
Short-term Functional Outcome in Psychotic Patients. Results of the Turku Early Psychosis Study (TEPS).
Authors: Salokangas Raimo K. R. , From Tiina , Ilonen Tuula , Luutonen Sinikka , Heinimaa Markus , Armio Reetta-Liina , Laurikainen Heikki , Walta Maija , Paju Janina , Toivonen Anna , Jalo Päivi , Tuominen Lauri , Hietala Jarmo
Published: April 2021

Background: Functional recovery of patients with clinical and sub-clinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known how these factors predict functional outcome in same models. We investigated functional outcome and its predictors in patients with first-episode psychosis (FEP) or confirmed vs. non-confirmed clinical high risk to psychosis (CHR-P vs. CHR-N). Methods: Altogether, 130 FEP, 60 CHR-P and 47 CHR-N patients were recruited and extensively examined at baseline (T0) and at 9 (T1) and 18 (T2) months after baseline. Global Assessment of Functioning (GAF) at T0, T1 and T2, and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcome was predicted in multivariate repeated ANOVA. Results: During follow-up, GAF improved significantly in FEP and CHR-P but not in CHR-N patients. In FEP, single marital status, low basic education, poor work situation, disorganised symptoms, perceptual deficits, and poor premorbid adjustment, in CHR-P, disorganised symptoms and poor premorbid adjustment and in CHR-N, low basic education, poor work situation and general symptoms predicted poor functional outcome. In FEP, psychotic symptoms at T1 and in CHR-P, psychotic and depression symptoms at T1 and anxiety symptoms at T2 associated with poor functioning. Conclusions: In FEP and CHR-P patients, poor premorbid adjustment and disorganised symptomatology are common predictors for functional outcome, while poor education and work situation predict poor functional outcome in FEP and CHR-N patients. Interventions aimed to improve studying and ability to work are most important in improving functioning of patients with clinical or subclinical psychosis.
Spatiotemporal Functional Modeling of Postseismic Deformation After the 2011 Tohoku-Oki Earthquake
Authors: Fujiwara Satoshi , Tobita Mikio , Ozawa Shinzaburo
Published: April 2021

Postseismic deformation continues for a long duration after major earthquakes. A previous study has shown that temporal changes in postseismic deformation can be approximated through simple functions. Almost 10 years have passed since the 2011 M9 Tohoku-Oki earthquake, and data at continuously operating global navigation satellite system stations have accumulated. We performed statistical processing of the data on postseismic deformations of this earthquake and obtained and verified their spatiotemporal distribution. We were able to approximate the postseismic deformations over a wide area with a standard deviation of 1 cm for approximately 10 years using two logarithmic and one exponential functions. However, the residuals from the functional model showed a sharp deviation from 2015. Although the pattern of postseismic deformation did not change after the earthquake, a change in steady-state velocity occurred from 2015 and continues till date. By improving the functional model to incorporate this steady-state velocity, we can reduce the overall standard deviation of the residuals of more than 200 stations distributed over more than 1000 km to less than 0.4 cm in the horizontal component. Furthermore, the spatial distributions of the coefficients of each time constant are not random and have a natural spread, which makes it possible to grid model them in terms of a spatial function. The spatial distributions of the short- and long-period components of the functional model and the afterslip and viscoelastic relaxation calculated by a physical model are similar to each other, respectively. Each time function has a meaning related to the physical processes in the underground, which provides an understanding of the physical phenomena involved in seismogenesis.
Usefulness of the Prostate Health Index in Predicting the Presence and Aggressiveness of Prostate Cancer Among Korean Men
Authors: Kim Jae-Yoon , Yu Ji-Hyeong , Sung Luck-Hee , Cho Dae-Yeon , Kim Hyun-Jung , Yoo Soo-Jin
Published: April 2021

BackgroundWe aimed to evaluate the usefulness of the Beckman Coulter prostate health index (PHI) and compare it with total prostate specific antigen (PSA) and related derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in the Korean population.MethodsA total of 140 men who underwent their first prostate biopsy for suspected PCa were included in this prospective observational study. The diagnostic performance of total PSA, free PSA, %free PSA, [–2] proPSA (p2PSA), %p2PSA, and PHI in detecting and predicting the aggressiveness of PCa was estimated using the receiver operating characteristic curve (ROC) and logistic multivariate regression analyses.ResultsOf 140 patients, PCa was detected in 63 (45%), and 48 (76.2%) of them had significant cancer with a Gleason score (GS) ≥7. In the whole group, the area under the curve (AUC) for ROC analysis of tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.63, 0.57, 0.69, 0.69, 0.71, and 0.75, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p = 0.005). For PCa with GS ≥7, the AUCs for tPSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI were 0.62, 0.58, 0.41, 0.79, 0.87, and 0.88, respectively, and the AUC was significantly greater in the PHI group than in the tPSA group (p < 0.001). In the subgroup with tPSA 4–10 ng/mL, both %p2PSA and PHI were strong independent predictors for PCa (p = 0.031, p = 0.027) and significantly improved the predictive accuracy of a base multivariable model including age, tPSA, and %fPSA, using multivariate logistic regression analysis. (p = 0.015, p = 0.010). Additionally, at a cutoff PHI value >33.4, unnecessary biopsy could be avoided in 22.9% (32/140) cases, with no aggressive cancer patients missed.ConclusionThis study shows that %p2PSA and PHI are superior to total PSA and %fPSA in predicting the presence and aggressiveness (GS≥7) of PCa among Korean men. Using PHI, a significant proportion of unnecessary biopsies can be avoided.
Impact of Covid-19 on urogenital online learning through WeChat in China
Authors: Zhang Peng , Wei Yongbao , Li Xin , Zhong Dewen , Song Wei , Wen Yanlin , Liu Longfei
Published: April 2021

Background

To evaluate the significance of social media and the impacts of Covid-19 on urogenital continuing education in China through WeChat.
Methods

Backend database from a Chinese urological online learning platform on account of WeChat named Jiujing before and during Covid-19 pandemic were compared and analyzed. An online questionnaire investigation containing 482 respondents was carried out to evaluate the impact of Covid-19 on urological online learning through WeChat.
Results

During the epidemic of Covid-19, the amounts of national subscribers in Jiujing platform increased by 26.24%, while the constituent ratio of subscribers’ quantity from Hubei province decreased although there were 189 new subscribers, and only surgery video section experienced increased constituent ratio of subscribers’ concerns. Online investigation indicated that most respondents experienced whittled offline learning opportunities and boosted online learning demands during Covid-19 pandemic as online learning was more efficiency, and these attitudes were associated with qualifications of the respondents. Surgery videos and academic lectures were the most popular sections. Preferences of the respondents were determined by gender, title, degree and affiliation hierarchy.
Conclusions

Even though the Covid-19 pandemic has affected the patterns of online medical education to a certain degree, continuing learning through social media like WeChat is essential and beneficial for urologists. Positional title, affiliation hierarchy and education background are supposed to impact their attitudes towards online learning.