Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative stress in breast and gynaecological carcinogenesis

Cancer is the leading cause of death worldwide. Despite the significant research effort, underlying mechanisms of carcinogenic processes are still poorly understood. In recent decades, a group of extremely reactive oxygen metabolites, reactive oxygen species (ROS), have been linked closely to carcinogenesis. Levels of ROS are constantly controlled by antioxidants to ensure stable redox balance in our cells. An aberrant cellular redox balance is thought to be connected to carcinogenesis by inflicting damage to cellular macromolecules and disturbing normal cellular signalling. In this work, the role of ROS in carcinogenesis was studied by observing the ROS-derived DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) in breast cancer and endometriosisassociated ovarian cancer. This marker was also measured in connection with endometriosis and PCOS to study the early stages of the carcinogenic process. In addition, peroxiredoxin antioxidant enzymes were studied in endometriosis-associated ovarian cancer to explore their impact on the carcinogenic process and relationship with ROS-derived DNA damage. There seems to be a decreasing trend in the expression of 8-OHdG in the development of breast cancer and endometriosis-associated ovarian cancer. In breast cancer, low levels of 8-OHdG in serum and in tumour tissue were found to be associated with more aggressive disease. In endometriosis-associated ovarian cancer, 8-OHdG and Prx II expressions in tissue decreased with malignant transformation from benign endometriosis tissue to ovarian cancer. Patients with PCOS were found to have lower levels of 8-OHdG in serum compared with healthy controls and metformin treatment further decreased 8-OHdG levels in obese patients. These results, together with observations is previous studies indicate that in breast cancer and endometriosis-associated ovarian cancer, a high level of ROS-derived DNA damage could be significant factor in the initiation stage of carcinogenesis, whereas in later stages carcinomas benefit from lower ROS levels that support tumour growth and survival via cellular signalling. In endometriosis, there seem to be high amounts of ROS-derived DNA damage, which could explain the increased ovarian cancer risk, while in PCOS, aberrant ROS levels could contribute to the pathogenesis of the disease itself and also to possible cancer incidence by inducing abnormal cellular signalling.
Successful Mobilization of Peripheral Blood Stem Cells After Intensive Bendamustine Pre-Treatment In Patients with Multiple Myeloma

Abstract 4439 Introduction The alkylating agent bendamustine has structural similarities to both alkylating agents and purine analogs, and is effective in the treatment of patients with multiple myeloma. So far, no data are available on stem cell toxicity or on stem cell mobilization. Since autologous stem cell transplantation is an established treatment for multiple myeloma after primary treatment, we were interested in analysing the experience of stem cell mobilization after bendamustine treatment. Material and Methods A retrospective analysis over a period of fifteen years was carried out in 56 (34 male and 22 female) patients with multiple myeloma after bendamustine pretreatment at the university hospitals Leipzig and Heidelberg. Patients had a median age of 58 (range 31–72) years. The median number of cycles was 3 (range 1–10) and the cumulative bendamustine dose ranged from 120 to 2400 mg/qm. The mobilization regimen in 37 cases was either cyclophosphamide 4 g/qm (n=33) or 7 g/qm (n=4) followed by G-CSF (2×5 ug/kg s.c.). Alternative regimens such as CAD, CED, TCED and others were used for mobilization in the remaining 19 patients. Apheresis was started as soon as peripheral blood CD34+ counts exceeded 10×106/l with a harvest target of 4×106 CD34+/kg using 4 times the blood volume. The minimal accepted target was 2×106 CD34+/kg. Results Stem cell harvest was successful in 54 of the 56 patients. In one patient the peripheral blood CD34+ cell count failed to reach 10 × 106/l and no apheresis was performed. In one further patient a rapid decrease in peripheral blood CD34+ counts resulted in insufficient recovery of stem cells in the apheresis product. In 18 out of 54 patients (33%) the target was reached with a single apharesis. The median number of aphareses in the 54 patients was 2 (range 1–7) and the median CD34+ cell-count obtained was 5.5 (range 1.7–20.4) × 106/kg. Engraftment was successful in 52/53 patients receiving a stem cell transplant. One patient was successfully harvested and did not receive the transplant yet. Conclusion From this retrospective analysis we conclude that mobilization of PBSC is possible after intensive bendamustine pretreatment. Disclosures: Niederwieser:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Goldschmidt:Celgene: Membership on an entity9s Board of Directors or advisory committees; Ortho Biotech: Membership on an entity9s Board of Directors or advisory committees; Ortho Biotech: Research Funding; Celgene: Research Funding; Chugai Pharma: Research Funding; Amgen: Research Funding.
A Case Report of Double Malignancy—Recurrent Nasopharyngeal Carcinoma and Adenocarcinoma of the Uterus

Multiple primary malignancies (MPMs) is a rare clinical condition where a patient is diagnosed with two or more cancers around the same time. Published literature reported the incidence of multiple primaries is in the range of 2% - 17%. The risk factors for MPMs are smoking, chronic alcoholism, genetic factors and previous treatment of cancer using radiotherapy that may lead to the development of other cancer. This case report describes a rare and unfortunate case of middle-aged Malaysian Chinese lady diagnosed with adenocarcinoma of the uterus and around the same time she had a recurrent nasopharyngeal carcinoma which was first diagnosed and treated 11 years ago. There were no clear risk factors identified in her and she defaulted follow up which eventually led to a fatal complication in which the nasopharyngeal cancer caused massive bleeding in her and she finally succumbed to the complication despite emergency resuscitations.
FREQUENCIES IN SAMPLES REFERRED TO PATHOLOGY LABORATORY OF AHWAZ UNIVERSITY OF MEDICAL SCIENCES FROM 2006 TO 2017

Breast cancer is the most common malignancy in women contributing to about 18% of all cancers worldwide. There are many well-known risk factors for breast cancer, and identifying these risk factors will help to reduce the mortality rate. This study is aimed to compare risk factors and the frequencies in women with benign and malignant breast tumor. This case-control study, was done with 60 women with benign breast tumors as controls and 60 women with malignant breast tumors as case They were randomly selected and checklist was made. Based on the information in the forms of pathology or from medical records or patient contact, data was completed. Data analysis was conducted using SPSS-16 statistical software. The results showed that the mean age at diagnosis (p_value=0.033), the frequency of positive family history of cancer (p_value=0.028) and the mean age at menarche (p_value=0.01) in the two groups was statistically significant difference. However, the frequency of having an abortion (p_value=0.391), the mean age of first child birth (p_value=0.641), the mean months of breastfeeding (p_value=0.281) and the frequency of having a perfect pregnancy (p_value=0.58) did not show significant difference between the two groups. The mean age at diagnosis and the frequency of positive family history of tumors in the case group, and the mean age of menarche in the control group is higher implication?
Indication and treatment of benign hepatic tumors

Background - Benign hepatic tumors occur in 9% of the population. The majority is diagnosed in asymptomatic patients during routine imaging exams. Aim - To present the main aspects of indications and treatment of benign hepatic tumors. Methods - A review was conducted based on literature search in PubMed, Scielo and Bireme crossing the headings liver cancer, hemangioma, adenoma and focal nodular hyperplasia. Was selected studies of surgical techniques and added the experience of the authors. Hemangioma is the most common hepatic tumor. It is identified in 5% to 7% of the autopsies. It is more common between the 3rd and 5th decades of the life and in female. This tumor may increase in size during pregnancy and with administration of sexual hormones. Although the etiology is not known, it is related with sexual hormones. Complications include inflammation, coagulopathy, bleeding and compression of neighboring organs. Spontaneous rupture is exceptional, with only 35 cases described in the literature. Adenoma and focal nodular hyperplasia are more common in young women, aged 20 to 40 years. Adenomas are treated by hepatic resection due to the risk of malignant transformation and bleeding. Focal nodular hyperplasia does not require treatment. Conclusions - The most common benign hepatic tumors are hemangioma, focal nodular hyperplasia, and adenoma. The differentiation between benign and malign tumors is usually based on clinical data and imaging exams. Hemangioma and focal nodular hyperplasia usually do not need treatment, while adenoma requires hepatic resection due to the risk of malignant transformation and bleeding. ABCDDV/819
Direct Solution of General ${\mathcal{H}}^2$ -Matrices With Controlled Accuracy and Concurrent Change of Cluster Bases for Electromagnetic Analysis

The dense matrix resulting from an integral equation (IE)-based solution of Maxwell’s equations can be compactly represented by an <inline-formula> <tex-math notation="LaTeX">${\mathcal H}^{2}$ </tex-math></inline-formula>-matrix with controlled accuracy. In this paper, we develop a new direct solution for general <inline-formula> <tex-math notation="LaTeX">${\mathcal H}^{2}$ </tex-math></inline-formula>-matrices. The new solution possesses not only explicitly controlled accuracy but also a full change of cluster basis to efficiently account for the updates to the original matrix during the direct solution procedure. The change of cluster basis is performed concurrently with the direct solution, without increasing its computational complexity. Comparisons with the state-of-the-art direct solutions have demonstrated a much reduced CPU run time of the new solution, in addition to a significantly improved accuracy, which is also controllable. Rapid and accurate direct solutions of millions of unknowns have been obtained on a single CPU core.
Importância das etapas pré-analíticas na dosagem de bicarbonato nos pacientes renais crônicos em hemodiálise

The purpose of the kidney is, among other things, to establish the acid-base balance in the healthy organism. In patients with chronic kidney disease, this regulatory mechanism is compromised, and it is common to observe metabolic acidosis in patients on conservative treatment and in patients with renal functional failure on hemodialysis. The relation between the increase of mortality in patients on dialysis and the presence of metabolic acidosis is a subject that has been studied, but the real extension of this problem in Brazil remains unknown. There are three methods currently being used for determination of bicarbonate: the analysis of arterial blood gases for determination of total pCO2, the method of alkaline reserve determination, which is already being abandoned, and the most recent, the enzymatic method. There still isn’t an appropriate laboratorial method for the evaluation of acidemia, since the blood exams there are collected in satellite clinics and later sent to the laboratory are influenced by the delay in transportation and examination, thus affecting the precision and accuracy of the results, considering the volatility of CO2. Therefore, we considered it useful to study the pre-analytical variables with the objective of improving at this stage so that the laboratory evaluation of metabolic acidosis is more accurate among hemodialysis patients. In this study, the analysis of arterial blood gases and the enzymatic method were compared, pursuing to establish which is the most convenient for measuring acid-base status in this specific group of patients. The importance of efficiency in performing the pre-analytical procedures was evident to guarantee greater accuracy for determination of bicarbonate in both methods. Waiting time did not significantly influence the obtained results by the compared methods, but the chemical method proved to be the most reliable, once it is a quantification method, different then the calculation to determinate bicarbonate values, as done in arterial blood gas analysis. Refrigeration shown to be efficient in the preservation of the samples in both methods. And centrifuge tubes for biochemical analysis has shown to be essential for the preservation of the biological sample in terms of avoiding hemolysis and possible interferents.
Avoiding perioperative oxygen debt

Perioperative management of high-risk surgical patients is a complex and complicated process. Hemodynamic instability can inflict vital organ hypoperfusion that can have several serious consequences, mainly due to cellular oxygen debt. Therefore, adequate monitoring guided early interventions are inevitable to avoid serious postoperative complications. However, conventional indices, including heart rate, blood pressure, skin temperature and urine output have limited value in diagnosing compensated shock. Therefore, advanced hemodynamic monitoring may become necessary when in addition to cardiac output other measures of oxygen delivery are also taken into account during treatment. However, any alteration that aims to affect macrocirculation only makes sense if it is followed by improved microcirculatory perfusion and adequate oxygen delivery to the cells. Putting the puzzle of hemodynamic stabilization together requires a complex, holistic approach. The purpose of this review is to discuss the holistic approach of multimodal, individualized monitoring that can help to avoid perioperative oxygen debt in high risk surgical patients.
Detection of Vowels in Speech Signals Degraded by Speech-Like Noise

Detecting vowels in a noisy speech signal is a very challenging task. The problem is further aggravated when the noise exhibits speech-like characteristics, e.g., babble noise. In this work, a novel front-end feature extraction technique exploiting variational mode decomposition (VMD) is proposed to improve the detection of vowels in speech data degraded by speech-like noise. Each short-time analysis frame of speech is first decomposed into a set of variational mode functions (VMFs) using VMD. The logarithmic energy present in each of the VMFs is then used as the front-end features for detecting vowels. A three-class classifier (vowel, non-vowel and silence) with acoustic modeling based on long short-term memory (LSTM) architecture is developed on the TIMIT database using the proposed features as well as mel-frequency cepstral coefficients (MFCC). Using the three-class classifier, frame-level time-alignments for a given speech utterance are obtained to detect the vowel regions. The proposed features result in significantly improved performance under noisy test conditions than the MFCC features. Further, the vowel regions detected using the proposed features are also quite different from those obtained through the MFCC. Exploiting the aforementioned differences, the evidences are combined to further improve the detection accuracy.
Aktuelle Konzepte zur Therapie des Schilddrüsenkarzinoms

Voraussetzung für die richtige Behandlung ist eine exakte pathologische Diagnose. Das ist an der Schilddrüse mitunter sehr kompliziert und beginnt schon beim Herausfiltern der seltenen Karzinome aus der Vielzahl der meist zufällig entdeckten harmlosen Schilddrüsenknoten, deren statistisches Malignitätsrisiko im Promillebereich liegt. Auch die Punktionszytologie erbringt nur vergleichsweise selten eine eindeutige Krebsdiagnose und unterliegt bei den häufigen follikulären Proliferationen einer hohen Interobserver-Variabilität [1].
Evaluation Of Micronuclei Using Papanicolaou And May Grunwald Giemsa Stain In Individuals With Different Tobacco Habits - A Comparative Study

Aims: To compare the Papanicolaou's (Pap) and May Grunwald's Giemsa (MGG) staining techniques which are done to detect micronuclei (MN) in exfoliated buccal mucosal cells in individuals with different tobacco habits. To determine the severity of human buccal cell changes which are associated with smoking and smokeless (''chewing'') tobacco (SLT). Methods and Material: A total of 45 male subjects (15 smokers, 15 smokeless tobacco users and 15 non users/ non smokers) were examined. Two cytological smears were taken from the apparently normal buccal mucosa from each individual. 45 smears (1 per individual) were wet fixed and stained with Pap and the remaining 45 smears were air dried and stained with the MGG stain. All the smears were assessed for cellularity and were scored for MN. Statistical analysis used: The ANOVA (one way analysis of variance) was used to analyse the frequency of cells with micronuclei. Bonferroni multiple comparisons were done to determine the significance (p<0.05) of the mean difference. Results: MNs were easily seen in the clear cytoplasm in the Pap smears. Regarding the MGG smears, bacteria and cell debris masked the effect of the MNs as compared to the Pap smears, where the fixative destroyed the bacteria and clearly demarcated the cell boundaries. The score of the MN frequency decreased as we moved from the smokeless tobacco chewers to the smokers and then to the non users and the non smokers. Conclusions: Pap is a better stain as compared to MGG for counting micronuclei. Smokeless tobacco chewers showed an increased number of MNs as compared to the smokers, thus laying emphasis on the greater carcinogenic potential of tobacco which was used in the chewable form.
Treatment of gliomatosis cerebri with temozolomide: A retrospective study of the AINO (Italian Association for Neuro- Oncology)

2033 Background: The optimal management for patients with primary gliomatosis cerebri is unknown, and some recent studies suggest that temozolomide could be useful as an upfront treatment. Methods: Between 1999 and 2005, 46 patients with biopsy proven gliomatosis cerebri were treated with temozolomide either upfront or at progression after prior radiotherapy/chemotherapy. Histological diagnoses were as follows: glioblastoma in 3 patients, malignant glioma in 8, anaplastic astrocytoma in 8, gemistocytic astrocytoma in 2, astrocytoma in 13, anaplastic oligodendroglioma in 1, anaplastic oligoastrocytoma in 1, oligoastrocytoma in 1, oligodendroglioma in 4, glial proliferation consistent with GC in 5. Median age was 49 years (range 14–70), with 20 males and 26 females and a median KPS at diagnosis of 80 (range 50–90). Twenty-three out of 46 (50%) pre-treatment MRI demonstrated some degree of contrast enhancement. Twenty-three of 46 patients were treated upfront, while 23 had received prior radiation therapy or.
E-Synthesis: A Bayesian Framework for Causal Assessment in Pharmacosurveillance

Background: Evidence suggesting adverse drug reactions often emerges unsystematically and unpredictably in form of anecdotal reports, case series and survey data. Safety trials and observational studies also provide crucial information regarding the (un-)safety of drugs. Hence, integrating multiple types of pharmacovigilance evidence is key to minimising the risks of harm. Methods: In previous work, we began the development of a Bayesian framework for aggregating multiple types of evidence to assess the probability of a putative causal link between drugs and side effects. This framework arose out of a philosophical analysis of the Bradford Hill Guidelines. In this article, we expand the Bayesian framework and add “evidential modulators,” which bear on the assessment of the reliability of incoming study results. The overall framework for evidence synthesis, “E-Synthesis”, is then applied to a case study. Results: Theoretically and computationally, E-Synthesis exploits coherence of partly or fully independent evidence converging towards the hypothesis of interest (or of conflicting evidence with respect to it), in order to update its posterior probability. With respect to other frameworks for evidence synthesis, our Bayesian model has the unique feature of grounding its inferential machinery on a consolidated theory of hypothesis confirmation (Bayesian epistemology), and in allowing any data from heterogeneous sources (cell-data, clinical trials, epidemiological studies), and methods (e.g., frequentist hypothesis testing, Bayesian adaptive trials, etc.) to be quantitatively integrated into the same inferential framework. Conclusions: E-Synthesis is highly flexible concerning the allowed input, while at the same time relying on a consistent computational system, that is philosophically and statistically grounded. Furthermore, by introducing evidential modulators, and thereby breaking up the different dimensions of evidence (strength, relevance, reliability), E-Synthesis allows them to be explicitly tracked in updating causal hypotheses.
Treatment of advanced neuroendocrine tumors: Results of the UKINETS and NCRI randomized phase II NET01 trial.

Background: Chemotherapy is widely used for advanced, unresectable neuroendocine tumours (NETs) but only four randomised trials are published. The first combined streptozocin (strep) and 5fluorouracil (5FU), reporting 63% response rate (RR), but subsequent retrospective studies had lower RRs (6-45%). Cisplatin has been combined with strep+5FU in a retrospective study with promising activity in NETs and capecitabine (cap) has been effectively substituted for 5FU in many tumours. The NET01 trial was designed to investigate whether cap+strep ± cisplatin warrant further evaluation. Methods: Patients (pts) with histologically confirmed, unresectable, advanced and/or metastatic NETs of foregut, pancreatic or unknown primary site were randomised (ratio 1:1) to 6 cycles of 3-weekly cap 625 mg/m2 po bd daily (D1-21), strep 1.0g/m2 IV (D1), with cisplatin 70mg/m2 IV(D1) (Cap-cist) or without (Cap-strep). The primary outcome measure was RR using RECIST criteria (v 1.0). 84 pts were required to test a RR of 60% with a significance level of 5% and 80% power in each arm. Central pathology review was performed; retrospective central radiology review was undertaken on 10% of randomly selected cases. Results: 86 pts (58% male, median age 59 years) were randomised (44 Cap-strep, 42 Cap-cist) with primary site – foregut 20%, pancreatic 48% and unknown 33%. The grade was low 8 (11%), intermediate 47 (67%) and high 15 (21%). Baseline characteristics were balanced between the 2 arms. 60% Cap-strep pts received ≥6 cycles compared with 33% Cap-cist pts. 17 Cap-strep and 26 Cap-cist pts experienced grade ≥3 toxicities. Outcome results are summarised in the table. Ki67, mitotic index or primary site of origin did not appear to predict for response. Conclusions: The novel Cap-strep ± cisplatin regimens were associated with overall disease control and survival durations consistent with published studies. Cap-strep was better tolerated than Cap-cist. Further prospective randomised studies are required to determine optimal NET chemotherapy