bluuebunny/crossref_metadata_2025 huggingface dataset:
LHX2 facilitates the progression of nasopharyngeal carcinoma via activating the autocrine secretion of FGF1
Authors: Xie Tao , Wang Baiyao , Zheng Jieling , Tian Yunhong , Li Rong , Huang Xiaoting , Lin Jie , Jian Haifeng , zhang Jian , Yuan Yawei
Published: October 2020

Background: Distant metastasis and recurrence remain the obstacle for nasopharyngeal carcinoma (NPC) treatment in clinical, unfortunately, the molecular events underlying NPC growth and metastasis are poorly understood. Methods: The expression level and prognostic value of LHX2 in pan-cancer were analized in TCGA database. The LHX2 expression both in protein and RNA levels in NPC tissues and normal tissues was determined by western blot, qRT-PCR and immunohistochemistry. The roles of LHX2 in oncogenesis were determined using CCK-8, colony formation assays, EdU assay, wound healing assays,transwell assay as well as in vivo mouse model.Bioinformatics analysis, the Gene Set Enrichment Analysis, Luciferase Reporter Assays and Chromatin Immunoprecipitation Assays were applied to identify the downstream effector of LHX2. The activation of indicated signal pathways were measured by western blot. Results: The LIM-homeodomain transcription factor 2 (LHX2) expression was increased in many solid tumors and was associated with poor progression based on the data from TCGA database.LHX2 levels was also significantly upregulated in NPC tissues and cell lines.Ectopic expression of LHX2 dramatically promoted the cell viability, colony formation efficiency, migratory and invasive ability of NPC cells both in vitro and in vivo. In mechanism, the Fibroblast Growth Factor 1 (FGF1) was confirmed transcriptionally regulated by LHX2 and mediated LHX2-induced tumor-promoting effects. The elevated expression of FGF1 by LHX2 activated the phosphorylation of STAT3, ERK1/2 and AKT/ser9-GSK3β/β-catenin signal pathway, leading to the increased proliferation ability and epithelial-to-mesenchymal transition (EMT). Treating NPC cells with FGF1-conditioned medium or human recombinant FGF1 accelerated tumor growth and metastasis, which could be blocked by tyrosine kinase inhibitor, AZD4547. \Conclusions: Our study provides mechanistic insight into how LHX2/FGF1 acts as a sufficient regulator pathway in NPC proliferation and metastasis, and the FGF1/FGFR1/2 trapping may contribute to the development of a novel target for NPC therapy.
Disaster Preparedness Should Represent an Augmentation of the Everyday Trauma System – But Are We Prepared?
Authors: Jørgensen Jørgen Joakim , Monrad-Hansen Peter Wiel , Gaarder Christine , Næss Pål Aksel
Published: October 2020

IntroductionMass casualty incidents (MCI) range from natural disasters to terrorist attacks. The increased frequency, geographical spread and the heterogenicity in type of terror incidents, challenge healthcare systems all over the world. Trauma systems constitute the base upon which disaster preparedness is being build. The largest MCI in Norway took place 22 July 2011 and several lessons were learnt including the importance of having designed the everyday trauma infrastructure to be able to increase activity and adjust according to needs. Norway is sparsely populated, with a national trauma system consisting of four regional trauma centers (TCs) and 35 acute care hospitals treating trauma (non-trauma centers; NTCs) We wanted to assess how well hospitals fill the national trauma system requirements for competence, and the degree of awareness of existing MCI plans.MethodsWe conducted a cross-sectional survey of the on-call trauma team in all 39 Norwegian hospitals during two time periods: July-August (HS; holiday season) and September – June (NHS; non-holiday season). A standardized questionnaire was used to evaluate the MCI preparedness.ResultsA total of 347 trauma team members participated with 173 during HS and 174 during NHS. Over 95% of the team members were aware of the hospital MCI plan, only half had read the plan during the last 6 months, whereas 63% at the TCs and 74% at NTCs were confident with their designated role in the event of an MCI. Trauma team exercises were conducted regularly and 86% had ever participated, primarily residents and nurses. Only 63% at the TCs and 53% at the NTCs had participated in an MCI exercise. The proportion of resident surgeons and anesthetists with >4 years clinical experience was significantly higher in TCs (88% and 63%) than in NTCs (27% and 17%). At NTCs 38% of the resident surgeons were on call from home after working hours. All the on-call consultant surgeons were at home after working hours, leaving interns in charge at several of the hospitals. All resident surgeons at the TCs were ATLS providers compared to 64% at the NTCs and almost 90% of the consultant surgeons had participated in advanced trauma surgical courses. ConclusionDespite increased focus on disaster preparedness at a national level after the 2011 attacks, we identified limited compliance with trauma system requirements concerning competency and training. Strict guidelines to secure immediate notification and early presence of consultants whenever a situation that might turn into an MCI occurs should be a prerequisite. The awareness and content of existing MCI plans should be continuously improved to be able to meet the challenges of future MCIs.
Efficacy and Safety of Luseogliflozin in Patient with Type 2 Diabetes Complicated by Hepatic Dysfunction
Authors: Seino Hiroaki
Published: October 2020

Background: Improvements in glycemic control and hepatic function are clinically important goals in the treatment of patients with type 2 diabetes mellitus complicated by hepatic dysfunction. The favorable effects of the sodium-glucose co-transporter inhibitor luseogliflozin on hepatic dysfunction were anticipated for humans. Nevertheless, few clinical studies have confirmed its real-world efficacy on hepatic dysfunction. This trial was conducted to assess the safety and efficacy of luseogliflozin in patients with type 2 diabetes mellitus complicated by hepatic dysfunction.Methods: This prospective, single-site, single-arm, open-label trial included 55 subjects. Subjects were administered with luseogliflozin and observed for 52 weeks. The primary endpoints were the change and percent change in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), and hemoglobin A1c (HbA1c) from baseline to week 52. The secondary endpoints included body weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), homeostatic model assessment beta (HOMA-β), homeostatic model assessment of insulin resistance (HOMA-IR), ferritin, Mac-2 binding protein (M2-BP), fatty liver index (FLI), fibrosis-4 (FIB-4) index, type IV collagen 7S domain, nonalcoholic fatty liver disease (NAFLD) fibrosis score, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6).Results: AST, ALT, γ-GTP, and HbA1c significantly decreased from baseline to week 52. Body weight, BMI, waist circumference, and FPG also significantly decreased. HOMA-IR significantly decreased but HOMA-β was unchanged. FLI, ferritin, M2-BP, and NAFLD fibrosis scores significantly decreased whereas the FIB-4 index and type IV collagen 7S domain did not significantly change. The hs-CRP and IL-6 levels did not significantly change.Conclusion: Luseogliflozin administration in T2DM patients with hepatic dysfunction was well tolerated, improved hepatic function, reduced liver fat, and attenuated liver injury and fibrosis. The present study might help establish a therapeutic approach for T2DM patients with hepatic dysfunction induced by SGLT2 inhibitors.Trial registration: This study was registered under the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (No. UMIN000025808) and the Japan Registry of Clinical Trials (No. jRCTs021180017).
Volumetric modulated arc therapy (VMAT) is superior to intensity modulated radiotherapy (IMRT) for liver sparing in SBRT for hepatocellular carcinoma
Authors: Kundel Yulia , Korzets Yasmin , Weinstock-Sabbah Miriam , Moore Assaf , Gordon Noa , Stemmer Salomon M. , Popovtzer Aaron , Brenner Baruch , Fenig Eyal , Allen Aaron M.
Published: October 2020

Background: The best delivery modality of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) from a technical point of view is still a matter of debate. The purpose of this study was to compare planning parameters with volumetric modulated arc therapy (VMAT) to static intensity modulated radiotherapy (IMRT) in treatment of HCC treated with SBRT. Methods: Twenty patients (pts) with localized HCC who were treated with SBRT were re-planned using two different radiation techniques: IMRT and VMAT. Patients with Child A cirrhosis received 45-54 Gy in 3 fractions and 5 pts with Child B cirrhosis received 30 Gy in 5 fractions. Planning was optimized to minimize doses to organs at risk (OAR) without compromising coverage of the planning treatment volume (PTV). VMAT and IMRT plans were compared using the conformity index (CI), homogeneity index of the PTV and monitor units (MUs) for time of treatment delivery, and other dose volume histogram (DVH) metrics.Results: The CI of VMAT plans were superior to those of IMRT(1.11±0.05 vs 1.18±0.06 (p <0.05) The MUs were significantly lower for VMAT (423.78±50.65) than for IMRT (890±160.68) (p <0.01). Stomach max dose, normal liver V15 Gy, normal liver mean dose were also decreased with VMAT planning. This was achieved without increased :V30 Gy of duodenum and small bowel , 10 cc(Gy) of duodenum, mean dose of right kidney and cord max dose . Conclusion: PTV coverage was more conformal with VMAT planning, with lower MUs and shorter delivery time compared to IMRT in all pts. Moreover VMAT planning was more effective than IMRT planning in the sparing of normal liver and stomach.
WITHDRAWN: Multimodal genetic features correlate with poor response to neoadjuvant chemoradiotherapy and high recurrence risk in Chinese patients with stage IB-IIA cervical cancer
Authors: Wei Yuchun , Wei Chuqing , Liang Chen , Liu Ning , Fang Zhenhao , Yin Jiani C. , Pang Jiaohui , Ou Qiuxiang , Wu Xue , Wang Xiaonan , Mu Dianbin , Shao Yang , Yu Jinming , Yuan Shuanghu
Published: October 2020

Background Response of cervical cancer patients to neoadjuvant therapy differs from person to person. It remains unclear whether genetic alterations can predict response to neoadjuvant therapy and disease-free survival in cervical cancer.Methods 62 Chinese patients with stage IB-IIA cervical cancer were included in this study. Pre-treatment tumor tissues were profiled using a targeted next-generation sequencing assay. Genetic alterations were compared with those identified in the Western populations using the TCGA database. Pathological response and disease-free survival (DFS) were evaluated and their correlations with genetic alterations were analyzed.Results Genetic alterations in PIK3CA were prevalent in both Chinese and Caucasian populations. The mutation frequencies of TERT, POLD1, NOS2, and FGFR3 were significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were frequently mutated in Caucasian patients. Germline mutations were identified in 13 out of 62 Chinese patients and 57% of them occurred in DNA repair genes, such as BRCA1/2, TP53 and PALB2. High tumor mutation burden (TMB), TP53 polymorphism (rs1042522) and KEAP1 mutations were found to be associated with poor response to neoadjuvant therapy. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC amplification and TYMS polymorphism were associated with higher relapse rates of cervical cancer.Conclusion The similarity and difference of mutation landscape of Chinese and Caucasian patients suggested genetic background played a role in shaping the architecture of cervical cancer mutations. The associations of mutation feature of cervical cancer with patient response and tumor recurrence risk provided rationale to further validate and explore potential biomarkers for cervical cancer patients.
Adding Pre-procedural Glycemia to the Mehran Score Enhances Its Ability to Predict Contrast-induced Acute Kidney Injury in Patients With and Without Diabetes Undergoing Percutaneous Coronary Intervention
Authors: Nusca Annunziata , Mangiacapra Fabio , Sticchi Alessandro , Polizzi Giovanni , D’Acunto Giulia , Ricottini Elisabetta , Melfi Rosetta , Gallo Paolo , Miglionico Marco , Giannone Sara , Ussia Gian Paolo , Grigioni Francesco
Published: October 2020

Background: The Mehran score is the most widely accepted tool for predicting contrast-induced acute kidney injury (CI-AKI), a major complication of percutaneous coronary intervention (PCI). Similarly, abnormal fasting pre-procedural glycemia (FPG) represents a modifiable risk factor for CI-AKI, but it is not included in current risk models for CI-AKI prediction. We sought to analyze whether adding FPG to the Mehran score improves its ability to predict CI-AKI following PCI.Methods: We analyzed 671 consecutive patients undergoing PCI (age 69 [63,75] years, 23% females), regardless of their diabetic status, to derive a revised Mehran score obtained by including FPG in the original Mehran score (Derivation Cohort). The new risk model (GlyMehr) was externally validated in 673 consecutive patients (Validation Cohort) (age 69 [62,76] years, 21% females). Results: In the Derivation Cohort, both FPG and the original Mehran score predicted CI-AKI (AUC 0.703 and 0.673, respectively). The GlyMehr score showed a better predictive ability when compared with the Mehran score both in the Derivation Cohort (AUC 0.749, 95%CI 0.662-0.836; p=0.0016) and the Validation Cohort (AUC 0.848, 95%CI, 0.792–0.903; p=0.0008). In the overall population (n=1344), the GlyMehr score confirmed its independent and incremental predictive ability regardless of diabetic status (p≤0.0034) or unstable/stable coronary syndromes (p≤0.0272). Conclusions: Adding FPG to the Mehran score significantly enhances our ability to predict CI-AKI. The GlyMehr score may contribute to improve the clinical management of patients undergoing PCI by identifying those at high risk of CI-AKI and potentially detecting modifiable risk factors.
Association between dietary lysine intake and lean body mass among young Indian women
Authors: Aggarwal Renuka , Bains Kiran , Kaur Harpreet
Published: October 2020

Background: Lysine is deficient in cereal based traditional Indian diets. Inadequate lysine intakes by Indian population may influence their lean body mass, thereby posing a risk to metabolic diseases and poor fitness. This study investigated associations between intakes of protein and lysine and its existing association with lean mass among Indian women. Methods: The study was carried out among 473 women. Dietary intake of protein and lysine was estimated via 24h recall. Lean body mass based on body composition analysis was assessed. Associations between intakes of protein and lysine with fat mass index, muscle mass index and fat free mass index were analyzed by Pearson's correlation coefficients. Results: Among women positive and significant associations were found between intake of lysine and muscle mass index(r=0.221) and fat free mass index(r= 0.371). An inverse association was found between fat mass index and lysine intake(r= - 0.278). Furthermore, the dietary adequacy for protein and lysine was only 71.88 and 39.41% against the recommended levels. Conclusions: Diets of the studied population was lacking in lysine. Among women, higher lysine intakes may decrease body fat gain and increase lean body mass suggesting better physical fitness and decreased risk of metabolic diseases.
Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases
Authors: Honda Hiroshi , Nishimichi Norihisa , Yamashita Michinori , Akimoto Yumiko , Tanimoto Hirotoshi , Teramoto Mitsue , Teramoto Hideki , Yokosaki Yasuyuki
Published: October 2020

Background: Endometriosis, which affects up to 10% women of reproductive age, is defined by the presence of ectopic endometrial tissue outside the uterus. The current key drug of hormonal therapies for endometriosis is dienogest, which is a progestin with high specificity for the progesterone receptor. Although many findings about the anti-endometriotic effect of dienogest on endometriosis have been reported, the precise mechanisms of dienogest's anti-endometriotic effect remain unknown. Methods: To investigate the direct anti-endometriotic effect of dienogest on endometriotic cells, we determined and compared the genome-wide gene expression profiles of endometriotic stromal cells treated with dienogest (Dienogest group) and those not treated with dienogest (Control group) and then performed a pathway analysis using these data. To test the microarray data, we performed real-time RT-PCRs for matrix metallopeptidase (MMP)-1, MMP-3, MMP-10, and TIMP-4.Results: Six-hundred forty-seven genes were revealed to be differentially expressed between the Dienogest and Control groups. Of them, 314 genes were upregulated and 333 genes were downregulated in the Dienogest group compared to the Control group. We identified 20 canonical pathways that are significantly distinct in the Dienogest group versus the Control group. Among the 20 canonical pathways, MMPs including MMP-1, -3, and -10 were found to be the most involved genes. Conclusions: Our results suggest that dienogest may exert its anti-endometriotic effect through the direct suppression of MMPs.
Outcomes of patients with End Stage Kidney Disease on dialysis with COVID-19. From PCR to Antibody.
Authors: Ahmed Wasim , Obaidli Ali Abdul Kareem Al , Joseph Princy , Smith Edward , Khan Ayaz Ahmad , Anwar Siddiq , Chandrasekar Thangavelu , Madani Ayman Kamal Al , Dastoor Hormazdiar Dara , Zahid Imran , Costales Freddie Agbayani , Boobes Yousef Abdul Rahim , Kindi Fatima Al , Issa Salah Eldin Khalil , Hassan Mohammed Hassan , George Abraham , Holt Stephen G
Published: October 2020

Background: End stage kidney disease patients on maintenance dialysis are vulnerable to contract COVID-19 infection and variable degrees of disease severity have been reported. SEHA Kidney Care (SKC) is the largest provider of dialysis services in the United Arab Emirates providing dialysis services to ~1180 patients, including ~80 patients on peritoneal dialysis. Mortality of COVID-19 among patients with ESKD on dialysis is high and ranges from 14 to 31% in different published series. Not much is known about antibody response to COVID-19 in this group of patients. Patient population demographics in the UAE are dissimilar to many other countries. The objective of this study was to describe the characteristics of patients and clinical staff who developed COVID-19 RT-PCR positivity and assess antibody response to COVID-19.Methods: We conducted a retrospective analysis to characterize features of COVID-19 in our adult dialysis population. In addition, IgG antibody serology was also performed to assess response to COVID-19. Results: The incidence of COVID-19 infection in our population was 13%. 81% of the patients were males, average age was 53.2 ± 12​ years, and 95% were on in-center haemodialysis. The majority of patients (68%) developed mild disease while 13% required critical care. Combinations of drugs including Hydroxychloroquine, Favipiravir, Lopinavir, Ritonavir, Camostat, Tocilizumab and steroids were used based on local guidelines. The median time to viral clearance was 15 days [IQR 6-26]. Overall mortality in our cohort was 9.2%.We performed COVID-19 IgG antibody serology in a subset (n=87) of RT-PCR positive patients. Interestingly, 23 (26%) patients did not develop any antibody response. We successfully implemented a regular screening strategy for patients and staff to identify asymptomatic carriers with an aim to isolate them from the rest of the cohort.Conclusions: Our study has highlighted an important finding of lack of antibody response in a quarter of patients with ESKD. This may have significant implications for this group of patients while efforts are underway to develop an effective vaccine against COVID-19. With regular screening of all dialysis patients and staff, asymptomatic carriers can be identified and prevent spread of COVID-19 within the dialysis units.
Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine
Authors: Liu Lu , Xu Xiaobai , Qu Zhengyang , Zhao Luopeng , Zhang Claire Shuiqing , Li Zhijuan , Lyu Tianli , Wang Xuefei , Jing Xianghong , Li Bin
Published: October 2020

Background: Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence Phosphorylation of protein kinase A (PKA)- or Extracellular signal-regulated kinase1/2 (ERK1/2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic Adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1/2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Methods: Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 minutes every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-days intervals during the 7-days injection protocol. The changes in 5-HT7R and 5-HT7R-mediated signaling pathway were examined by real time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analyses.Results: When compared with IS group, mechanical and thermal pain thresholds of the IS+EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS+EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1/2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1/2. Conclusion: Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1/2 in TG and TNC.
The Effects of Public Health Emergencies on Altruistic Behaviors: Empirical Research on the COVID-19 Pandemic in China
Authors: Jin Xiaotong , Huang Ershuai , Song Wei , Zhao Taiyang
Published: October 2020

Background: The coronavirus disease 2019 (COVID-19) pandemic constitutes a public health emergency that threatens all of society. During this time, it is important for people to help each other by providing support related to the viral components of the pandemic while also assisting with difficulties experienced at the social level. However, the nature of the infection itself puts everyone at risk, which may prevent altruistic behaviors. In other words, the pandemic has created a dilemma in which individuals may need to choose between their personal safety and continuing to help others. As such, this study explored how public health emergencies affect altruistic behaviors in the context of COVID-19.Methods: Questionnaire surveys were distributed to 1508 residents from 31 provinces across China in February 2020 during the outbreak of COVID-19. Structural equation models were then implemented to test multiple research hypotheses using the obtained data.Results: Findings showed that the severity of the pandemic had both positive and negative effects on altruistic behaviors. Empathy mediated the positive relationship between the severity of the pandemic and altruistic behavior, while the sense of control mediated the negative effect between the severity of the pandemic and altruistic behavior.Conclusions: In the context of public emergencies such as the COVID-19 pandemic, altruistic behaviors can be enhanced by strengthening the factors of empathy and sense of control. These findings are useful for a government’s altruistic behavior promotion and disaster risk management.
Indiferencija i opuštenost
Authors: Barbarić Damir
Published: October 2020

U članku se nastoji istražiti i što preciznije odrediti višestruko složeni odnos Heideggerova mišljenja spram Schellingove filozofije. Od početne fascinacije Schellingovim središnjim spisom o slobodi, u kojem nalazi značajne analogije s vlastitim pokušajima promišljanja konačnosti slobode, a time i samog bitka, Heidegger će se u daljnjem razvijanju vlastita mišljenja od Schellinga sve više i sve oštrije distancirati, prigovarajući mu da ne uspijeva prevladati metafiziku, već ostaje u njezinu vidokrugu, premda na izniman i u svakom pogledu respektabilan način. Primjerenost te prosudbe u članku se stavlja u pitanje i svestrano propituje kritičkom usporedbom i temeljitom pojmovnom analizom Schellingova shvaćanja volje, indiferencije, ljubavi i ekstaze s jedne, te Heideggerova shvaćanja zla, volje za voljom, bezdana i opuštenosti s druge strane. Pritom na vidjelo zaključno izlazi stvarna srodnost tih središnjih pojmova kasne filozofije jednog i drugog mislioca, koja je mnogo veća nego što je to Heidegger bio spreman uvidjeti i iskoristiti za krajnje svrhe vlastita mišljenja.
Povijesno-filozofijski horizont i oblikovanje pojma prirode u Schellingovu Spisu o slobodi
Authors: Baksa Goran
Published: October 2020

Spis o slobodi predstavlja prekretnicu u Schellingovoj filozofiji. Već je filozofijom prirode Schelling napravio otklon od strogih idealističkih okvira, prvenstveno Kanta i Fichtea, jer je za sistematsko utemeljenje cjelokupnog znanja nužan identitet subjekta i objekta tražio u samome objektu kao momentu djelatnosti samopostavljanja apsolutnog subjekta, no tek je sa Spisom o slobodi istupio iz tog okvira. Riječ je o uvođenju drugog principa, koji je komplementaran, ali nesvodiv na standardni idealistički princip samosvijesti. Radi se o temelju ili prirodi u Bogu. Tek se kroz to dvojstvo principa mogao zahvatiti pozitivan pojam slobode kao mogućnosti za dobro i zlo. Tako cjelovito pojmljena činjenica ljudske slobode povezala se s cjelinom bića. Svrha takvog objašnjenja bio je pokušaj odgovora na problem koji se protezao kroz cijelo Schellingovo filozofiranje – odnos konačnog i beskonačnog.
The effect of atom losses on the distribution of rapidities in the one-dimensional Bose gas
Authors: Bouchoule Isabelle , Doyon Benjamin , Dubail Jerome
Published: October 2020

We theoretically investigate the effect of atom losses in the
one-dimensional (1D) Bose gas with repulsive contact interactions, a
famous quantum integrable system also known as the Lieb-Liniger gas. The
generic case of KK-body
losses (K=1,2,3,\dotsK=1,2,3,…)
is considered. We assume that the loss rate is much smaller than the
rate of intrinsic relaxation of the system, so that at any time the
state of the system is captured by its rapidity distribution (or,
equivalently, by a Generalized Gibbs Ensemble). We give the equation
governing the time evolution of the rapidity distribution and we propose
a general numerical procedure to solve it. In the asymptotic regimes of
vanishing repulsion – where the gas behaves like an ideal Bose gas – and
hard-core repulsion – where the gas is mapped to a non-interacting Fermi
gas –, we derive analytic formulas. In the latter case, our analytic
result shows that losses affect the rapidity distribution in a
non-trivial way, the time derivative of the rapidity distribution being
both non-linear and non-local in rapidity space.
El papel de los recursos humanos en la prevención de errores médicos para la mejora en el sistema de calidad hospitalaria
Authors: Reyes Berlanga Mónica Lucía , López-Lemus Jorge Armando , Vargas Chanes Delfino , De La Garza Carranza María Teresa
Published: October 2020

Introducción: El objetivo de la presente investigación fue identificar la influencia conjunta que ejercen los recursos humanos a través de la cultura clan, el compromiso hacia la organización, y los errores médicos sobre el sistema de calidad en hospitales públicos y privados. Por lo tanto, se buscó determinar si existe una relación significativa entre el compromiso afectivo, el compromiso normativo, los errores médicos reportados y su impacto en el sistema de calidad de organizaciones hospitalarias del estado de Guanajuato, México.Método: Se tomó una muestra de 311 médicos y enfermeras de manera aleatoria en cuatro diferentes hospitales del estado de Guanajuato. Primero, se calcularon los métodos estadísticos necesarios para probar la validez y confiabilidad de los cuestionarios de las variables antes mencionadas. En un segundo lugar, se realizó un modelo estadístico, basado en la técnica de ecuaciones estructurales para identificar la relación entre las variables estudiadas. Para este fin se utilizó el software estadísticos AMOS v.21.Resultados: Para el primer paso especificado en el método, se validaron los cuestionarios con los parámetros establecidos para este fin (CFI, TLI, RMSEA y alpha de Cronbach). Para la prueba del modelo hipotético diseñado, que comprende los factores involucrados en el estudio, los resultados muestran una relación significativa entre las variables de cultura tipo clan y el compromiso afectivo (β = 0.62, p<0.00) y normativo (β = 0.43, p<0.00); y entre el compromiso afectivo y los errores médicos reportados (β = 0.27, p<0.00). Finalmente se muestra una relación entre los errores médicos reportados y el sistema de calidad afectivo (β = 0.85, p<0.00).Discusión o Conclusión: Se demuestra que la cultura organizacional es un factor importante, de mucha influencia para el compromiso del personal de los hospitales. Este compromiso organizacional es un detonador para la mejora del sistema de calidad, a través del reporte correcto de los errores médicos.
The Use of Molecular Docking and Spectroscopic Methods for Investigation of The Interaction Between Regorafenib with Human Serum Albumin (HSA) and Calf Thymus DNA (Ct-DNA) In The Presence Of Different Site Markers
Authors: Tanzadehpanah Hamid , Mahaki Hanie , Moradi Mohammadreza , Afshar Saeid , Moghadam Neda Hosseinpour , Salehzadeh Sadegh , Najafi Rezvan , Amini Razieh , Saidijam Massoud
Published: October 2020

Background:

Interactions of drugs with DNA and proteins may modify their biological
activities and conformations, which effect transport and biological metabolism of drugs.

Objective:

In this study the interaction of anticancer drug regorafenib (REG) with calf thymus-DNA
(ct-DNA) and human serum albumin (HSA) has been investigated

Methods:

Hence, for the first time, it was discovered interaction between REG with DNA and
HSA using multi-spectroscopic, zeta potential measurements and molecular docking method.

Results and Discussion:

DNA displacement studies showed that REG does not have any effect on
acridine orange and methylene blue bound DNA, though it was substantiated by displacement
studies with Hoechst (as groove binder). Furthermore, the different concentrations of REG induce
slight changes in the viscosity of ct-DNA. Zeta potential parameters indicated that hydrophobic interaction
plays a major role in the DNA-REG complex. Results obtained from molecular docking
demonstrate that the REG prefers to bind on the minor groove of DNAs than that of the major
groove. Binding properties of HSA reveal that intrinsic fluorescence of HSA could be quenched by
REG in a static mode. The competitive experiments in the presence of warfarin and ibuprofen (as
site markers) suggested that the binding site of REG to HSA was most probably located in the subdomain
IIA. Measurements of the zeta potential indicated that REG bound to HSA mainly by both
electrostatic and hydrophobic interactions. It was found on docking procedures that REG could fit
well into HSA subdomain IIA, which confirmed the experimental results.

Conclusion:

In conclusion, REG can be delivered by HSA in a circulatory system and affect DNA
as potential target.
In-silico Studies and Biological Activity of Potential BACE-1 Inhibitors
Authors: Arya Richa , Paliwal Sarvesh , Gupta Satya P. , Sharma Swapnil , Madan Kirtika , Mishra Achal , Verma Kanika , Chauhan Neha
Published: October 2020

Background:

Alzheimer’s disease is neurological condition causing cognitive inability and dementia. The pathological lesions and neuronal damage in brain is caused by self-aggregated fragments of mutated Amyloidal precursor protein (APP).

Objective: :

The controlled APP processing by inhibition of secretase is the strategy to reduce Aβ load to treat Alzheimer’s disease.

Method:

A QSAR study was performed on 55 Pyrrolidine based ligands as BACE-1 inhibitors with activity magnitude of greater than 4.of compounds.

Results:

In an advent to design new BACE-1 inhibitors, the pharmacophore model with correlation (r = 0.90) and root mean square deviation (RMSD) of 0.87 was developed and validated. Further, the hits retrieved by in-silico approach were evaluated by docking interactions.

Conclusion:

Two structurally diverse compounds exhibited Asp32 and Thr232 binding with the BACE-1 receptor. The aryl substituted carbamate compound exhibited highest fit value and docking score. The biological activity evaluation by in-vitro assay was found to be >0.1µM.
Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis
Authors: Galati Giovanni , Massimo Vainieri Antonio Fabio , Maria Fulgenzi Claudia Angela , Di Donato Stefano , Silletta Marianna , Gallo Paolo , Onorato Angelo , Vespasiani-Gentilucci Umberto , Picardi Antonio
Published: October 2020

Background:

Hepatocellular carcinoma (HCC) is among the world’s most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).

Aim:

The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways.

Methods:

The Food and Drug Administration (FDA)’s and European Medicines Agency (EMA)’s datasheets, results from clinical trials and observational studies have been reviewed.

Results:

This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients.

Conclusions:

The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.
Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma
Authors: Wang Yingyi , Jin Bao , Zhou Na , Sun Zhao , Li Jiayi , Chen Qiao , Wu Xiangan , Zhou Yi , Shi Yue , Lu Xin , Sang Xinting , Mao Yilei , Du Shunda , Wang Wenze , Bai Chunmei
Published: October 2020

Background:

Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined.

Objective:

The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival.

Methods:

We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry.

Results:

Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration.

Conclusion:

We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.
Diagnosis of Renal Diseases Based on Machine Learning Methods Using Ultrasound Images
Authors: Li Guanghan , Liu Jian , Wu Jingping , Tian Yan , Ma Liyong , Liu Yuejun , Zhang Bo , Mou Shan , Zheng Min
Published: October 2020

Background:

The incidence rate of renal disease is high, which can cause end-stage renal
disease. Ultrasound is a commonly used imaging method, including conventional ultrasound,
color ultrasound, elastography, etc. Machine learning is a potential method which has been widely
used in clinical practices.

Objective:

To compare the diagnostic performance of different ultrasonic image measurement parameters
for kidney diseases, and to compare different machine learning methods with the human-
reading method.

Methods:

Ninety-four patients with pathologically diagnosed renal diseases and 109 normal controls
were included in this study. The patients were examined by conventional ultrasound, color ultrasound
and shear wave elasticity, respectively. Ultrasonic data were analyzed by Support vector
machine (SVM), random forest (RF), K-nearest neighbor (KNN) and artificial neural network (ANN),
respectively, and compared with the human-reading method.

Results:

Only ultrasound elastography data have a diagnostic value for renal diseases. The accuracy
of SVM, RF, KNN and ANN methods is 80.98%, 80.32%, 78.03% and 79.67%, respectively,
while the accuracy of human-reading is 78.33%. In the data of machine learning ultrasound elastography,
the elastic hardness parameters of the renal cortex are most important.

Conclusion:

Ultrasound elastography is of the highest diagnostic value in machine learning for
nephropathy, the diagnostic efficiency of the machine learning method is slightly higher than that
of the human-reading method, and the diagnostic ability of the SVM method is higher than other
methods.
Efficacy and Cardiovascular Safety of SGLT2 Inhibitors
Authors: Fernandez Cornelius James , Nevins Abisha Graciano , Nawaz Shasta , Nazir Tahir , Hanna Fahmy W.F.
Published: October 2020

Patients with diabetes continued to exhibit a high risk for cardiovascular and renal
events despite achieving satisfactory glycemic, blood pressure and lipid targets. Studies evaluating
new diabetes medications focused on cardiovascular events, largely overlooking heart failure (HF).
The latter has recently been recognised as a major cause of morbidity and mortality in patients with
diabetes mellitus. There had been an unmet need for drugs with cardiovascular (including HF) and
renal protection, with an expectation that an ideal diabetic drug should improve these endpoints.
Moreover, an ideal drug should have weight reducing benefits. Recently published outcome trials
have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor
agonists (GLP-1RAs) can reduce cardiovascular and renal events, together with statistically
significant weight reduction. As a result, many recently published international guidelines have recommended
SGLT2 inhibitors and GLP-1RAs in patients with diabetes and pre-existing cardiovascular
disease (CVD). In this review, we will critically analyse the efficacy and cardiovascular (CV)
safety of SGLT2 inhibitors, based on the available literature to help position them in the clinical decision
process.
Maternal Sodium Valproate Exposure Alters Neuroendocrine-Cytokines and Oxido-inflammatory Axes in Neonatal Albino Rats
Authors: A-G Neama , AM El-bakry , EH Rasha , Ahmed RG
Published: October 2020

Objective:

The aim of the study was to determine the influence of maternal sodium valproate
(SVP) on neonatal neuroendocrine (hypothalamic-pituitary-adrenal; HPA)-cytokines and
oxido-inflammatory axes.

Methods:

Pregnant rats (Rattus norvegicus) were orally administered (by gavage) SVP (50 mg/kg)
from gestation day (GD) 8 to lactation day (LD) 21.

Results:

The elevation in serum corticotropin-releasing hormone (CRH), corticosterone, and
adrenocorticotropic hormone (ACTH) levels was highly significant at postnatal days (PNDs) 14
and 21 in both dams and neonates of the maternal SVP-treated group relative to those in the control
group. However, hypercortisolism (cortisolemia) was highly significant in neonates at both PNDs
14 and 21, while in dams, it was not significantly increased at LD 14 but was at LD 21. This disruption
caused adverse effects on maternal food consumption and maternal/neonatal body weight. The
maternal SVP treatment resulted in higher levels of neonatal serum adrenaline, noradrenaline, neuropeptide
Y (NPY), tumor necrosis factor-alpha (TNF-α), leptin, interleukins (IL-1β, IL-17, IL-4,
IL-6 & IL-2), transforming growth factor-beta (TGF-β), and prostaglandin E2 (PGE2), and lower
levels of neonatal serum growth hormone (GH), insulin growth factor-1 (IGF-1) and adiponectin at
both PNDs. This administration also induced the oxidative stress in neonatal cerebrum and cerebellum
at both tested PNDs via the production of free radicals (malondialdehyde; MDA & nitric
oxide; NO) and reduction of antioxidant parameters (glutathione; GSH, superoxide dismutase;
SOD & catalase; CAT).

Conclusion:

Maternal SVP treatment stimulated the neonatal stress-brain (HPA) axis, resulted in
an oxido-inflammatory state, and disrupted the neuroendocrine-cytokines axis, and generally neonatal
health.
Investigation of Structural and Thermoelectric Properties of Bismuth Selenide Thin Films
Authors: Sharma Harsha , Sharma Yogesh Chandra
Published: October 2020

Background:

Thermoelectric material with high performance and low cost is
the basic need of today. Bismuth selenide is a thermoelectric material. A set of bismuth
selenide thin films having different stoichiometry ratios varying Bi/Se ratio from 0.123 to
0.309 have been prepared.

Objective:

The present work deals with the synthesis and characterization of various thin
films of bismuth selenide. The thermoelectric properties of thin films were also investigated.
The aim of this work is to investigate the effect of composition ratio on the structural
and thermoelectric properties and to find out the best stoichiometry ratio of bismuth selenide
thin films that can be used in the application of thermoelectric devices.

Methods::

A set of bismuth selenide thin films having different elemental compositions
were prepared by employing the thermal evaporation technique. The crystal structure and
elemental composition of thin films were investigated by XRD and EDAX, respectively.
The roughness of films was analyzed by AFM. The thermoelectric properties of various
thin films were also measured.

Results:

XRD spectrum confirms the formation of phases formed in thin films which
slightly matched with standard data. AFM results indicated that the surface of films was
smooth and nanoparticles were generated on the surface. AFM results indicated that the
surfaces of annealed thin films were smoother than as-deposited thin films. Seebeck coefficient
was found negative throughout the temperature range. The power factor was also
calculated by the Seebeck coefficient and results revealed the effect of composition ratio
on Seebeck coefficient, electrical conductivity, and power factor. Thin films having a
composition ratio of 0.182 exhibited the highest power factor.

Conclusion:

This study provides relevant basic information on the thermoelectric property
of thin films, as well as presents the effect of compositional variation on thermoelectric
measurements. From the application point of view in the thermoelectric devices, the best
stoichiometric thin films out of four prepared thin films have been presented.
Civic teacher strategy in the integration of nationalism and tolerance character in school based on pesantren in Yogyakarta city
Authors: Benaziria Benaziria , Murdiono Mukhamad
Published: October 2020

This research aims to determine the strategy of civic education teachers in integrating nationalist character and tolerance in Junior High School based on pesantren in Yogyakarta City. Research type used in this research is qualitative research with case study method. The research subjects consisted of teachers of civic education who taught at Junior High School based on pesantren in Yogyakarta City. The research data was collected through semi-structured interview, observation and documentation. Data analysis using qualitative analysis techniques, namely data reduction, data presentation and conclusion. Data validity uses two forms of triangulation, ie source triangulation and engineering triangulation. The result of the research is that teachers have integrated nationalist character and tolerance into learning planning and implementation. Learning strategies used to integrate nationalist character and tolerance are lecture method, question and answer, and assignment. Media and learning resources used in the form of books, and video or picture display. This study finds that the implementation of civic education learning done by teachers is not based on lesson planning and effective lecture method is used as a learning strategy if teachers use media and learning resources such as video shows, slide point power usage of the media can increase the enthusiasm of learners.
History and promotion of a culture of peace at global level through education
Authors: Mehta Kunal
Published: October 2020

This article is concerned with the great task before the United Nations: saving future generations from the scourge of war. This entails the transformation not only of the institutional structures and manifestations of war, but also of the deeply rooted culture of violence and war, and the evolution of a culture of peace and non-violence. It provides a brief history of the concept of the culture of peace, discusses the basic aspects of the concept, and reflects on its relationship with everyday life. It then outlines the various actions undertaken by UNESCO during 1992–8 to promote a culture of peace, and lists declarations for a culture of peace and non-violence.