Miracle-dz/UniFAR-FTUs huggingface dataset:
EV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer.

TPS4593 Background: PD-(L)1-targeted immune checkpoint inhibitors (CPIs), such as pembrolizumab (P), are approved for patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) who progress after platinum, are ineligible for first-line (1L) cisplatin (PD-L1 positive), or are ineligible for 1L platinum. The ORR for CPI in all treated pts is ~25%, and a combination approach may provide additional benefit. Enfortumab vedotin (EV), an investigational antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to cells expressing Nectin-4, found in 97% of mUC pt samples (Petrylak ASCO 2017). In a phase 1 study (NCT02091999), EV (1.25 mg/kg) was generally well tolerated with a confirmed ORR of 43% in 112 mUC pts (Rosenberg ASCO-GU 2019). These encouraging results, with the potential for an enhanced immune response, suggest that EV+P may improve response rates and extend response durability. Methods: EV-103, a phase 1b trial for non–resectable la/mUC pts with no prior CPI, added an additional 4 cohorts (Parts 2 and 3) in an Oct 2018 amendment. It is now expected to enroll ~159 pts. Dose escalation pts (EV+P, 1L or 2L) must be ineligible for 1L cisplatin-based chemotherapy or have disease progression during/following treatment with ≥1 platinum-containing regimen. Dose expansion (Part 1) will evaluate EV+P in 1L (Cohort A) and 2L settings (Optional Cohort B). Part 2 will evaluate 1L EV+cisplatin (Cohort D), 1L EV+carboplatin (Cohort E), and 1L or 2L EV+gemcitabine (Optional Cohort F). Part 3 (Cohort G) will evaluate 1L EV+P+cisplatin or carboplatin, depending on pts cisplatin-eligibility. In all cohorts, pts receive EV on Days 1 and 8 of each 3-week cycle. In combination therapies, pts receive P, cisplatin, and carboplatin on Day 1 or gemcitabine on Days 1 and 8 of each cycle. The primary objective is to assess the safety/tolerability of EV+P and/or chemotherapy. Secondary objectives are establishing EV recommended dose for combination therapies, assessing ORR per RECIST for all cohorts and per iRECIST for therapies with pembrolizumab, as well as assessing disease control rate, duration of response, PFS, OS, PK, and biomarkers. The study opened Oct 2017. Clinical trial information: NCT03288545.
Cholelithiasis: causative factors, clinical manifestations and management

Background: Cholelithiasis is a common gastrointestinal disorder with an overall prevalence of 2-29%. This study aims to evaluate the evolution of demographic and etiological factors, the clinical manifestations of Cholelithiasis, the surgical management with its post-operative complications and the histopathological findings of the post-cholecystectomy specimen of gallbladder, in central India.Methods: Patients symptomatic or asymptomatic diagnosed ultrasonically as cholelithiasis were included in the study and patients with primary choledocholithiasis were excluded.Results: A total of 92 patients were enrolled, of which 62 (68.89%) were female, with mean age of 45.03yrs ± 13.59. Fifty four patients (58.69%) were having BMI >25. Pain was most common complaint seen in all patients. Jaundice was observed in 13 patients (14.13%) who had associated CBD calculus. Sickling was positive in 8.69% of patients. Lap cholecystectomy was done in 71 (77.17%) patients with a conversion rate of 6.57%. Nineteen (20.65%) were open cholecystectomy with or without CBD exploration and 2 underwent Lap cholecystostomy. Post operatively, surgical site infection was seen in 3 patients (4.22%) of laparoscopic cholecystectomy, 5 patients (26.31%) of open cholecystectomy and biliary leak was seen in 3 patients (15.78%) of open cholecystectomy. Histopathology of gallbladder was chronic cholecystitis in 70 patients (77.77%), malignancy was detected in 5 patients (5.55%) and Xanthogranulomatous cholecystitis in 2 patients (2.22%). Conclusions: Cholelithiasis is commonly seen in females in 4th and 5th decade mainly presenting with abdominal pain and dyspepsia. Laparoscopic cholecystectomy offers best surgical management with lesser complications.
Participatory school health education on vector-borne diseases: engaging children as change agents

Vector-borne diseases contribute substantially to the global burden of diseases and disproportionately affect poor and under-served populations living in a country like India. Children can be effective change agents of health in their schools, peer groups, families and communities. We evaluated the effectiveness of participatory school health education on vector-borne diseases among 200 high school children, 100 each from government and private schools. Questions regarding vector-borne diseases, mosquito breeding sites, diseases transmitted by them and mosquito control measures were used to assess their knowledge before and after a health education intervention. Education included lecture, role play and community-based group activity. Average overall pretest score was 11.8 ± 5.03 which increased significantly to 19.3 ± 4.69 after intervention. Health education showed significant improvement in knowledge irrespective of type of school, gender or class of study. It was observed that private school children, girls and 10th class students' post-test scores were significantly better than their counter groups. Participatory school-based health education improved the knowledge of children regarding vector-borne diseases. This could be an effective medium in promoting health and possibly behavioural changes in the community. Such school-based vector-borne disease control could be applied to developing countries where there is good school enrolment and attendance.
The Educative Role of an Animal Care Committee in Canada: A Case Study

Animal Care Committees (ACCs) in Canada operate within guidelines established by the Canadian Council on Animal Care, an autonomous advisory and supervisory body sponsored by the Association of Universities and Colleges of Canada. ACCs are established to ensure appropriate, humane use of animals in research and teaching, including the adoption of valid alternatives. Their role includes an educative responsibility: to ensure that both ACC members and scientists using animals are acquainted with the ethical issues surrounding animal use and principles relating to refinement of techniques, reduction of numbers used and replacement where possible.Strategies employed by one university ACC consistent with these aims are described and evaluated. Qualitative and quantitative data are presented derived from participant observation by the author as an ACC member, committee protocols, minutes and other records and a survey of animal users ‘ perceptions of the role and value of the ACC. Results indicated a relatively low level of familiarity with ethical principles relating to the humane treatment of animals, although regulations governing housing and care were well known.
The Making of Modern Romanian Culture: Literacy and the Development of National Identity

This book challenges the notion that Western ideas were essential to Romanian development. It is a fascinating story of how a national culture is born. This book provides a history of the development of literary culture and the printed word in Romania. How do literacy and the development of literary culture promote the development of a national identity? "The Making of Modern Romanian Culture" examines the development of both a literary tradition and institutions aimed at promoting literacy in Romania in the eighteenth and nineteenth centuries - from Romanians under the control of the Austrian Empire in the eighteenth century to revolt in Romania under Tudor Vladimirescu in 1821 to Carol, the first King of Romania, crowned in 1881. Alex Drace-Francis combines analysis of education systems, book production, and the periodical press with case studies of key thinkers such as Mihai Eminescu, Ion Luca Caragiale and Titu Maiorescu to trace Romania's cultural and literary development. He offers a criticism of the idea that the 'penetration of Western ideas' was essential to modernism to place literacy and identity within both a Romanian and a global context.
Measuring the Long-Term Outcomes of Traumatic Brain Injury: A Review of the Community Integration Questionnaire

The Community Integration Questionnaire (CIQ) was developed as a measure of reassumption of roles, responsibilities, and relationships by persons with traumatic brain injury (TBI). In this article, data from a number of studies relevant to the CIQ's psychometric qualities (reliability, sensitivity, validity, and subscore and total score distributions) are summarized, and its scope, content validity, metric, norms, and age and gender effects on scores are discussed. Recommendations are made for the use of the CIQ, and for research needed to improve the utility of the current measure as well as to develop a better one.
A Novel Multicriteria Approach – Rough Step-Wise Weight Assessment Ratio Analysis Method (R-SWARA) and Its Application in Logistics

A decision-making process often requires knowledge of numerous parameters and their interaction in order to make valid decisions that will result in meeting the objectives set. Multi-criteria decision-making is an area that helps in decision-making processes considering a set of criteria and alternatives. A new MCDM approach has been developed in this paper with a view to better managing the uncertainties and the subjectivity of real decision problems. In the last few years, the integration of Rough numbers and multi-criteria decision-making methods has enjoyed a great popularity, so in this paper, the Rough Step-wise Weight Assessment Ratio Analysis (SWARA) approach has been developed. The developed approach has been verified throughout a sensitivity analysis, which involves the comparison of the obtained results with two other methods for determining the weight values, the Rough Best Worst method (BWM) and Rough Analytic Hierarchy Process (AHP). The correlation of obtained ranks using the Rough SWARA approach with the ranks of Rough BWM and Rough AHP is complete, i.e. the ranks are identical, which confirms the stability and credibility of the developed approach.
Study of Serum Magnesium Levels in Types 2 Diabetes Mellitus

Background And Objectives: Diabetes mellitus was one of the most common metabolic disorder and leading cause of death and disability in the world. The incidence of diabetes was increasing in India and globally. Several studies have shown that low serum magnesium concentrations in Type 2 diabetics compared to healthy controls. Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity in patients with Type 2 diabetes. Magnesium deficiency can lead to development of complications such as retinopathy, thrombosis and hypertension. Hence this study was conducted at Tertiary care center in Aurangabad Maharashtra. Methods: A study was done in randomly chosen 100 Type 2 diabetic patients, and 100 non diabetic age / sex matched controls age group 30 to 70 years attending diabetic clinic at M.G. M. Medical College And Hospital Aurangabad. All patients and controls underwent thorough clinical examination and estimation of serum magnesium, FBS, PPBS, lipid profile and urea, creatinine levels. Results: 37% of diabetic patients had low serum magnesium levels (Mglevel<1.5mg/dL) and 9% of controls had low serum magnesium levels (Mg 2+ level<1.5mg/dL). The mean serum magnesium levels were 1.96=0.54mg/dL and 2.375+0.449mg/dL, in diabetics and controls respectively (p value < 0.0001 Highly significant). There is negative co relationship between Sr.Mg Levels and hypertension and there was also found to be negative correlation between Mg and retinopathy. In the study hypomagnesaemia (Mg 2+ level < 1.5mg/dl) is correlating with hypertension hence there is an association between hypertension and serum Mg 2+ level (p=0.018 highly significant). Hypomagnesaemia (Mg2+ Level < 1.5mg/dL) is correlating with retinopathy In this study hence there is an association between retinopathy and serum M g2 + level p:0.041 significant) Interpretation And Conclusion: This study demonstrated that Low Mg status is common in Type 2 diabetes mellitus patients when compared to non diabetic controls. It may be prudent in clinical practice to periodically monitor plasma Mg 2+ concentration in diabetic patients. If plasma Mg 2+ is low, an intervention to increase dietary intake of magnesium maybe beneficial.
Treatment of breast cancer: dealing with toxicity

Two of the major challenges in breast cancer research are to increase efficacy of anticancer treatments without increasing clinical relevant toxicity and/or to decrease toxicity of anticancer treatment without decreasing its efficacy. To achieve this, improved insight into the mechanisms underlying treatment-induced toxicity is crucial. This thesis describes studies in which it is aimed to optimize therapy for patients with breast cancer in various stages of the disease. This might be reached by dealing with toxicity in several ways: (1) decreasing toxicity, while maintaining efficacy, (2) increasing efficacy, without increasing clinical relevant toxicity, (3) increasing efficacy by toxicity-based dose escalation and (4) prevention of (complications of ) toxicity of anticancer treatments.
Mining biomarkers of epilepsy from large-scale intracranial electroencephalography

MINING BIOMARKERS OF EPILEPSY FROM LARGE-SCALE INTRACRANIAL ELECTROENCEPHALOGRAPHY Hoameng Ung Brian Litt, M.D. Epilepsy is a chronic neurological disorder characterized by seizures. Affecting over 65 million people worldwide, the quality of life of a patient with uncontrolled epilepsy is further degraded by medical, social, cognitive, and psychological dysfunction. Fortunately, two-thirds of these patients can achieve adequate seizure control through medications. Unfortunately, one-third cannot. Improving treatment for this patient population depends upon improving our understanding of the underlying epileptic network. Clinical therapies modulate this network to some degree of success, including surgery to remove the seizure onset zone or neuromodulation to alter the brain’s dynamics. High resolution intracranial EEG (iEEG) is often employed to study the dynamics of cortical networks, from interictal patterns to more complex quantitative features. These interictal patterns include epileptiform biomarkers whose detection and mapping, along with seizures and neuroimaging, form the mainstay of data for clinical decision making around drug therapy, surgery, and devices. They are also increasingly important to assess the effects of epileptic physiology on brain functions like behavior and cognition, which are not well characterized. In this work, we investigate the significance and trends of epileptiform biomarkers in animal and human models of epilepsy. We develop reliable methods to quantify interictal patterns, applying state of the art techniques from machine learning, signal processing, and EEG analysis. We then validate these tools in three major applications: 1. We study the effect of interictal spikes on human cognition, 2. We assess trends of interictal epileptiform bursts and their relationship to seizures in recordings from canines and rats, and 3. We assess the stability of long-term iEEG spanning several years. These findings have two main impacts: (1) they inform the interpretation of interictal iEEG patterns and elucidate the timescale of post-implantation changes. These findings have important implications for research and clinical care, particularly implantable devices and evaluating patients for epilepsy surgery. (2) They provide an analytical framework to enable others to mine largescale iEEG datasets. In this way we hope to make a lasting contribution to accelerate collaborative research not only in epilepsy, but also in the study of animal and human electrophysiology in acute and chronic conditions.
Dominant Lactic Acid Bacteria in Naturally Fermented Milks from Messinese Goat’s Breed

Background: Lactic Acid Bacteria (LAB) are an important group of microorganisms responsible for the fermentation dairy products. This study was done to identify the dominant lactic acid bacteria in naturally fermented milks from Messinese goat’s breed. Methods: Eighteen individual raw milk samples collected from Messinese goat’s breed were acidified at pH 5.20 and left to spontaneously ferment at 37 °C for 4 days. All samples were analyzed for rod- and coccus-shaped LAB. Also, all presumptive LAB were isolated and differentiated according to their phenotypic properties and genetic polymorphisms and then identified by sequencing the 16S rRNA gene. Data were statistically analyzed using SAS 9.2 software. Results: Levels of coccus- and rod-shaped LAB were in the range of 1.78-7.10 log and 1.00-7.09 log colony forming unit/ml, respectively. The microbiological counts on the two different growth media were significantly (p<0.05) different among the samples. Among 12 identified strains, the most numerous one was Enterococcus hirae (n=4), followed by E. faecium (n=3), while the other species (E. durans, E. faecalis, E. lactis, Lactococcus lactis, and Leuconostoc lactis) included one strain each. Conclusion: The major group identified in this study was mainly represented by members of Enterococcus genus. Although Enterococcus spp. are related to the typicality of some traditional fermented dairy products, this study highlights the need for risk assessment of pathogenic enterococci species for the consumers.
The Spectacle: Media and the Making of the O.J. Simpson Story

Introduction Murder in Los Angeles Bundy and Rockingham The Chase Frenzy in L.A. The Greatest Story Ever Metamorphosis The Race Card Judge Ito and the Media The Great Camera Debate Media Wars The Trial of O. J. Simpson Firestorm Exposed House of Mirrors The Journalists The Fuhrman Trial The Black and White Press Closing Curtain Judgment Day Aftermath Prologue Index
Does PD1/PDL1 Immunotherapy Require Patient Tumor Subgroup Pre-Analysis in the Era of Precision Medicine?

Inter-individual variability of the therapeutic response of patients with cancer to anti-PD1 immunotherapy is a determinant for precision medicine. Anti-PD1 monoclonal antibodies (mAb) interact with the PD1 receptor expressed on T cells, hence prevent-ing the recognition of PDL1 ligand on tumor cells and enhancing their cytotoxic effect. The Food & Drug Administration (FDA) as well as the European Medicines Agency (EMA) have approved anti-PD1 mAb for several human cancer therapies, including malignant melanoma, non-small cell lung cancer, renal cancer, urothelial cancer, and Hodgkin’s lymphoma. Anti-PD1 mAb can increase overall survival or progression free survival, but in some subgroups of patients they have shown lower or no therapeutic effect. In recent years, expression levels of PDL1 in tumor cells have been recognized as a determinant for predicting the responsiveness to anti-PD1 mAb therapy, however other factors such as age, or somatic mutations might also play a role. Here we propose the pre-evaluation of PD1 receptor expression status as a prerequisite for patient selection for treatment with anti-PD1 mAb-based therapy.
Interim analysis of the fierce-21 phase 2 (P2) study of vofatamab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).

4547 Background: Patients (pts) with mUC with FGFR3 mutations who have failed platinum-based chemotherapy have a poor prognosis. Their response to immune checkpoint inhibitors appears diminished 10% or less compared to WT pts. 20% of mUC pts harbor FGFR3 mutations or fusions (M/F). Vofatamab is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. FIERCE-21 is a Phase 1b/2 study designed to evaluate vofatamab monotherapy (VFM) or in combination with docetaxel (VFD). Methods: The P2 expansion enrolled mUC pts with FGFR3 M/F+ tumor (identified with FoundationONE CDx™), who failed ≥ 1 prior line of chemotherapy (including prior taxane for pts receiving VFM) or recurred ≤ 12 months of (neo)adjuvant chemotherapy. Pts had measurable disease and ECOG ≤ 1. Treatment consisted of vofatamab at 25 mg/kg alone and in combination with docetaxel at 75 mg/m2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and objective response-rate (ORR). Results: In the P2, 21 pts each received VFM and VFD. 57% of VFD pts had received at least 2, and 71% of VFM at least 3 prior lines of therapy. Best response to prior therapy was PD for 67% of VFD and 38% of VFM. The safety profile is consistent with previously reported data. TEAEs occurring in > 20% of pts were decreased appetite, diarrhea, pyrexia, asthenia, anemia, dyspnea, and fatigue. Most common vofatamab-related TEAEs in > 10% of pts were asthenia, diarrhea, decreased appetite and rash; all were Grade 1 or 2. In VFM, only 1 pt had a grade 3 TEAE and no pt discontinued treatment due to an AE. There were no cases of hyperphosphatemia, ocular or nail toxicity; 1 pt reported grade 2 skin toxicity. For pts receiving VM, median age was 70 yrs, ECOG 1 = 67%, Hgb < 10 g/dL 5%, liver metastases 19%. Responses have been seen in 7 pts to date including those receiving both VFM and VFD. Conclusions: Vofatamab both alone and combined with D in a q3w schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VFM and VFD have demonstrated efficacy in terms of ORR. PFS/OS and DOR data will be presented at 7+ months for VFD and 9+ months for VFM. Clinical trial information: NCT02401542.
Effects of glycerol in the refolding and unfolding of creatine kinase

The effects of glycerol in the refolding, reactivation, unfolding, and inactivation of guanidine denatured creatine kinase were studied by observing the fluorescence emission spectra and the circular dichroism spectra, and by recovery and inactivation of enzymatic activity and aggregation. The results show that low concentrations of glycerol (25%) improve the refolding yields of creatine kinase, but high glycerol concentrations decrease its recovery. Glycerol favors the secondary structural formation and inhibits aggregation of creatine kinase as proline does. These systematic observations further support the suggestion that low concentrations of glycerol possibly play a chaperone role in the refolding of creatine kinase. In addition, glycerol reduces the inactivation and unfolding rate of creatine kinase, increases the change in transition free energy of unfolding (ΔΔG u) and stabilizes its active conformation relative to the partially unfolded state with no glycerol. In the presence of glycerol, the inactivation and unfolding dynamics of creatine kinase are related to glycerol concentrations. Glycerol blocks the exposure of hydrophobic areas and the dissociation of dimers, and protects creatine kinase against guanidine denaturation in a concentration dependent manner. This study suggests that glycerol as an energy substrate for metabolism and organic components in vivo, assists correct protein folding, maintains adequate rates of enzymatic catalysis and stabilizes the protein secondary and tertiary conformations. 