Classic Hodgkin Lymphoma Refractory for ABVD Treatment Is Characterized by Pathologically Activated Signal Transduction Pathways as Revealed by Proteomic Profiling

In classic Hodgkin lymphoma (cHL), the tumour microenvironment (TME) is of major pathological relevance. The paucity of neoplastic cells makes it important to study the entire TME when searching for prognostic biomarkers. Cure rates in cHL have improved markedly over the last several decades, but patients with primary refractory disease still show inferior survival. We performed a proteomic comparison of pretreatment tumour tissue from ABVD treatment-refractory versus ABVD treatment-sensitive cHL patients, in order to identify biological differences correlating with treatment outcome. Formalin-fixed paraffin-embedded tumour tissues from 36 patients with cHL, 15 with treatment-refractory disease, and 21 with treatment-sensitive disease, were processed for proteomic investigation. Label-free quantification nano liquid chromatography tandem mass spectrometry was performed on the tissues. A total of 3920 proteins were detected and quantified between the refractory and sensitive groups. This comparison revealed several subtle but significant differences in protein expression which could identify subcluster characteristics of the refractory group. Bioinformatic analysis of the biological differences indicated that a number of pathologically activated signal transduction pathways are disturbed in ABVD treatment-refractory cHL.

ANALISIS PERAN PEREMPUAN DALAM MENANAMKAN NILAI-NILAI PENDIDIKAN ISLAM TERHADAP ANAK

All human beings are creatures of the one God. They are equal, regardless of cultural background. Therefore, they receive the same appreciation from God and that must be respected and glorified. Thus, discrimination based on gender, skin color, class, race, ethnicity, religion, and so on has no basis at all in the teachings of Tawhid. Only the level of taqwa to Allah is the measure of the difference. The concepts of biological and sociocultural differences between men and women view that biological differences between the two are considered natural, while social differences are considered cultural. Whatever the background of these differences, it is not a reason to justify each other because women have the same rights as men in all fields, including education, economy, social, culture, even law and defense and state security. Women deserve special rights. Women should have important roles as well as recognition in various aspects of life. Education for women is very important. Educating women is a fundamental and critical necessity, so they can play their role properly and correctly and give contribution as productive members of the society.

КОМУНИКАЦИОНЕН ОКТАГОН: АСПЕКТИ НА ИНТЕЛИГЕНТНОСТТА ПРЕЗ ПРИЗМАТА НА КОМУНИКАЦИОННАТА СРЕДА

The aim of the paper is to highlight certain aspects of the semantic profile of the concept of "intelligence" through a model called "communication octagon", focusing on the theory of dynamics of communication links, and to analyze the interaction between the intelligent system and the social environment. The focus of interest in the study is human intelligence, based on individual biological differences, which can be modified as a result of construction and transmission of knowledge, mutual emotional transfer, making cognitive requirements (directed inwards and outwards, towards the environment), and as a result of dynamic social interactions.

A Significance of Land Cover - Why Wisents Succeed to Outlive Aurochs?

Context Two native European large herbivores: the aurochs (Bos primigenius) and the wisent (Bison bonasus) lived simultaneously until late Medieval Ages. A rapid decline of aurochs occurred between XV and VII centuries, while wisents lived in the wild until early XX century. Aurochs went extinct despite their strict protection, imposed by Polish kings. Since XV century, radical changes in land cover occurred all over Europe, which could influence the survival of those species. Objectives We aimed to present differences in geographical distribution and occurrence of aurochs and wisents, and identify major changes in land cover of Europe since Medieval Ages. Considering those, we were trying to explain differences in the survival of so closely related and biologically similar species. Methods We compared distribution and incidence of traditional geographical names associated with both species in central-eastern Europe, with historical changes in land cover there. Considering biological differences between aurochs and wisents we attempted to identify possible reasons for such difference in their survival. Results Since aurochs were predominantly true grazers, having higher preference towards open landscapes, they apparently were stronger affected by the loss of suitable habitats due to the development of agriculture. Wisents being more flexible could survive in forests avoiding encounters and conflicts with people. Conclusions Changes in land cover may be critical for the survival of endangered species, even strictly protected. This issue has to be seriously considered in nature conservation planning and in the evaluation of habitat quality for wildlife.

Computerised analysis of writing and drawing by essential tremor phenotype

We investigated whether computerised analysis of writing and drawing could discriminate essential tremor (ET) phenotypes according to the 2018 Consensus Statement on the Classification of Tremors. The Consensus scheme emphasises soft additional findings, mainly motor, that do not suffice to diagnose another tremor syndrome. Ten men and nine women were classified by blinded assessors according to Consensus Axis 1 definitions of ET and ET plus. Blinded scoring of tremor severity and alternating limb movement was also conducted. Twenty healthy participants acted as controls. Four writing and three drawing tasks were performed on a Wacom Intuos Pro Large digital tablet with a pressure-sensor mounted ink pen. Sixty-seven computerised measurements were obtained, comprising static (dimensional and temporal), kinematic and pen pressure features. The mean age of ET participants was 67.2±13.0 years and mean tremor duration was 21.7±19.0 years. Six were classified as ET, five had one plus feature and eight had two plus features. The computerised analysis could predict the presence and number of ET plus features. Measures of acceleration and variation of pen pressure performed strongly to separate ET phenotypes (p<0.05). Plus features were associated with higher scores on the Fahn-Tolosa-Marin Tremor Rating Scale (p=0.001) and it appeared that ET groups were mainly being separated according to severity of tremor and by compensatory manoeuvres used by participants with more severe tremor. There were, in addition, a small number of negative kinematic correlations suggesting some slowness with ET plus. Abnormal repetitive limb movement was also correlated with tremor severity (R=0.57) by clinical grading. Critics of the Consensus Statement have drawn attention to weaknesses of the ET plus concept in relation to duration and severity of ET. This classification of ET may be too biased towards tremor severity to assist in distinguishing underlying biological differences by clinical measurement.

Scientific Racism Attitudes Among Diverse Undergraduate Pre–Health Professions Students

Scientific racism, or the belief that racial hierarchies are explained by biological differences, among health care professionals may contribute to the oversight of social causes of health problems and result in poor quality of care. This study examines the extent to which scientific racism may permeate undergraduate pre–health professions student worldviews before entering advanced training. Undergraduate students ( n = 251) pursuing training in health professions from The University of Texas at San Antonio completed a survey in 2018 measuring respondent level of agreement with statements about biological differences between U.S. racial and ethnic groups, as well as agreement with statements about cognitive differences, health behaviors, and systemic racism. Analyses showed that the students agreed with false statements regarding biological, behavioral, and cognitive differences among races and agreement was significantly stronger among students at earlier stages of education but did not differ by student race/ethnicity. Adjusted analyses showed that third- and fourth-year undergraduate students exhibited less agreement with false statements about race than first- and second-year students ([Formula: see text] 95% CI [−18.33, −3.39], p < .00). The joint effect of higher class level and public health major ([Formula: see text] 95% CI [−11.98, −1.16], p = .02) was also significantly associated with less agreement with false statements regarding systemic racism. This exploratory study suggests that even among diverse student populations, scientific racism persists but may improve over educational careers. Future research may determine how structural reforms and training can further improve student understandings of race as a social construct and not a biological reality.

The Old Man and the Meat: On Gender Differences in Meat Consumption across Stages of Human Life

It is not a radically new insight that men eat more meat than women do. However, one piece of the puzzle was previously missing: the development of a gender bias in total and red meat consumption across stages of human life. To identify the gender bias across stages of human life, we apply a multiple-group regression across seven age classes. Data for the empirical analysis stem from the US National Health and Nutrition Examination Survey. Regression results reveal that gender differences in meat consumption start only after the age of four and then move in some parallel with the development of biological differences, reaching a maximum between 51 and 65 years. The effect of both household income and education on meat consumption is negative and per-capita consumption of meat rises with household size.

Candidate genes of SARS-CoV-2 gender susceptibility

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) initiated a global viral pandemic since late 2019. Understanding that Coronavirus disease (COVID-19) disproportionately affects men than women results in great challenges. Although there is a growing body of published study on this topic, effective explanations underlying these sex differences and their effects on the infection outcome still remain uncertain. We applied a holistic bioinformatics method to investigate molecular variations of known SARS-CoV-2 interacting human proteins mainly expressed in gonadal tissues (testis and ovary), allowing for the identification of potential genetic targets for this infection. Functional enrichment and interaction network analyses were also performed to better investigate the biological differences between testicular and ovarian responses in the SARS-CoV-2 infection, paying particular attention to genes linked to immune-related pathways, reactions of host cells after intracellular infection, steroid hormone biosynthesis, receptor signaling, and the complement cascade, in order to evaluate their potential association with sexual difference in the likelihood of infection and severity of symptoms. The analysis revealed that within the testis network TMPRSS2, ADAM10, SERPING1, and CCR5 were present, while within the ovary network we found BST2, GATA1, ENPEP, TLR4, TLR7, IRF1, and IRF2. Our findings could provide potential targets for forthcoming experimental investigation related to SARS-CoV-2 treatment.

Genomic Heterogeneity Contributed To The Different Survival Between Adult and Pediatric Acute Lymphoblastic Leukemia

Prognosis of acute lymphoblastic leukemia (ALL) in adults is inferior to children. Hence, ALL is still a challenging disease to be cured in adult population. Aberrant genetic alterations have been observed previously in ALL, while the patterns of differential gene alteration have not much been comprehensively determined in the adult and pediatric ALL on a genome-wide scale. This study was attempted to investigate the biological differences in genomic profiling between the adults and children with ALL, and the relationship between the genomic heterogeneity and prognosis. The results showed the similar common mutation types in two populations but the increased prevalence of genetic alterations in adult ALL. The median number of detected gene mutations was 17 (range: 1–53) per sample in adult ALL and 4.5 (range: 1–19) in pediatric ALL(P<0.001). A significant correlation between the increased number of gene mutations and age was found (R2 = 0.5853, P<0.001). 122 and 53 driver genes were identified in adult and pediatric ALL samples, respectively. The IKZF1, IDH1 and TTN mutations were significantly enriched in adult ALL. The incidence of relapse was 40.0% and 9.6% in the adult and pediatric ALL, respectively(P=0.0003). The overall survival (OS) and relapse free survival (RFS) of adult ALL were poorer than pediatric ALL (P=0.0002, P<0.001, respectively). This genomic landscape enhanced the understanding of the biological differences of ALL between the two populations and provided a clue for novel therapeutic approaches.

DDRE-28. IDENTIFICATION OF SYNERGISTIC DRUG COMBINATIONS FOR THE THERAPY OF IDHmut GLIOMA

OBJECTIVE Isocitrate Dehydrogenase (IDH) mutation in glioma results in a multitude of biological differences with consequences for survival and therapy response. Therefore, IDH mutated (IDHmut) and wildtype (IDHwt) tumors are regarded as separate entities with the need for adjusted therapy like the combination of procarbazine, CCNU and vincristine (PCV). However, as vincristine has often severe side effects like neuropathy new effective therapy options are required. Therefore, we searched for combinations of FDA-approved drugs which effectively inhibit the growth of IDHmut cells in vitro. METHODS We tested different drug combinations of a drug library consisting of 146 FDA-approved drugs on two established IDHmut GSC lines. Based on a previous single agent drug screen, six drugs were selected (Idarubicin, Ixazumib, Ponatinib, Neratinib, Romidepsin) to be combined with all 146 drugs of the library. Cell viability was assessed by the CellTiterGlo 3D assay (Promega) in 96 well plates, while Caspase-Glo 3/7 3D assay was used to measure induction of apoptosis. RESULTS Out of 1460 drug combinations tested altogether 21 synergistic drug combinations could be identified and validated. The combination with the highest blood-brain-barrier permeability score was further investigated. Finally, drug-concentrations elucidating the highest synergistic effect on proliferation was further studied in a 8-point dose-response matrix followed by validation in additional four IDHmut GSC lines. CONCLUSION This work can lay the foundation for future improvements of the therapy of patients suffering from LGGs.