Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of colorectal cancer patients treated on ETCTN 10021: A multicenter randomized trial of combined PD-L1 and CTLA-4 inhibition with targeted low-dose or hypofractionated radiation.

49 Background: Pre-clinical and clinical evidence support immune effects of targeted radiation (RT) resulting in synergy with immune checkpoint therapy. However, prospective data are lacking in regards to safety, efficacy and immunologic impacts of different doses of RT given in conjunction with PD-L1 and CTLA-4 blockade. Methods: ETCTN 10021 is a multicenter randomized phase 2 study evaluating repeated low-dose fractionated RT (LDFRT) or hypofractionated RT (HFRT) in combination with PD-L1 and CTLA-4 inhibition in metastatic microsatellite-stable colorectal cancer (CRC) refractory to first-line chemotherapy, or non-small cell lung cancer progressive on prior PD-1 inhibition. The primary endpoint is objective response excluding irradiated lesions. Pre- and on-treatment biopsies were analyzed using multiplex immunofluorescence (IF) evaluating multiple immune markers. We report the prespecified analysis of the CRC cohort. Results: Twenty CRC patients were randomized, 19 of whom were treated with immunotherapy and RT, and 18 of whom were evaluable for response. Median lines of prior therapy were 4 (range 1-7). There were 16 patients with toxicity potentially related to treatment (84%), and 8 patients with possibly associated grade 3-5 toxicity (42%). Best response was stable disease in one patient with an abscopal out-of-field response who developed new lesions after HFRT and 4 cycles with decreasing overall disease burden. Correlative IF performed on 5 sample pairs revealed that HFRT, but not LDFRT, increased infiltration of CD8+, and CD8+/PD1+/Ki67+ T-cells in the RT field. Conclusions: We demonstrate the feasibility of a multicenter randomized study adding different RT regimens to PD-L1/CTLA-4 blockade. Toxicity was, in general, consistent with PD-L1/CTLA-4 inhibition with no significant RT-related toxicities noted. Although the best response of stable disease doesn’t support the use of PD-L1/CTLA-4 inhibition with HFRT or LDFRT in this population using these RT regimens and schedule, integrated biomarkers provide support that HFRT impacts the local immune microenvironment. Clinical trial information: NCT02888743.
Brucellosis Presenting as Cholecystitis: A Case Report and Literature Review

Abstract Brucellosis is a zoonotic disease endemic to much of the world. It most often presents with nonspecific symptoms and is a well known cause of undulant fever. Focal forms occur less frequently, with osteoarticular complications being the most common. In this study, we describe a rare case of brucellosis presenting as cholecystitis.
Impact of DNA Repair Gene Polymorphisms (XPD and XRCC1) on the Risk of Breast Cancer in Egyptian Female Patients

The genes involved in DNA repair system play a crucial role in the protection against mutations . It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. There are multiple pathways to repair the different types of DNA damage and maintain genomic integrity among them is the nucleotide excision repair (NER) and the base excision repair (BER) pathways. Aim & methods: The aim of the present study was to examine the relation between the DNA repair gene polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinico-pathological parameters of BC and also to investigate the synergistic effect of both genes on BC susceptibility . Both XPD and XRCC1 polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system -polymerase chain reaction (PCR) (ARMS) method and PCR with confronting two-pair primers(PCR–CTPP) , using DNA from peripheral blood in a case control study. RESULTS: our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the breast cancer study patients than in the normal individuals(p≤0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing breast cancer Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease Finally ,the combination of AA(XPD)+AG(XRCC1) were significantly associated with breast cancer risk. In conclusion, the present results suggest that, XPD gene is an important candidate gene for susceptibility to breast cancer. Also, gene–gene interaction between XPD(AA)+XRCC1(AG) polymorphism may be associated with increased risk of breast cancer in Egyptian women.
The relationship between serum levels of lipid profile and activity of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis. It is the most common form of chronic inflammatory arthritis and often results in joint damage and physical disability. As it is a systemic disease, it may result in variety of extra-articular manifestations, including fatigue, subcutaneous nodules, lung involvement, pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities. Aim of the work: Show changes of serum lipid profile in patients with rheumatoid arthritis. Patients and Methods: Fifty patients with rheumatoid arthritis who diagnosed according to (EULAR/ ACR2010) criteria for rheumatoid arthritis, 47 females and 3 males with a mean age of 36.80 ±6.03 years. Fifty control healthy subjects included 43 females and 7 males with a mean age of 36.14 ±7.73 years were examined for their lipid profile parameters and disease activity. Lipid profile parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and atherogenic index ratio), erythrocyte sedimentation rate and C-reactive protein; all were determined for both the patients and control groups. Results: The results of the present study revealed that rheumatoid arthritis patients exhibited a highly significant increase in total cholesterol and low-density lipoprotein cholesterol (p=0.0001), with a significant increase in high-density lipoprotein cholesterol (p= 0.002). As a consequence, the atherogenic index ratio was significantly higher (p=0.0001). The rheumatoid factor, CRP and ESR were higher in patients with RA than in control group with very highly significant difference (p=0.0001). There is a significant correlation between disease activity score (DAS 28) and different parameters of lipid profile which was a highly significant with LDL and TC/HDL (0.9-0.8) respectively and was less significant with other parameters. The disease duration for rheumatoid arthritis patients was significantly correlated with Das28 score (p=0.01). Conclusion: Rheumatoid arthritis patients are characterized by an atherogenic lipid profile in comparison with the healthy controls. Recognition and treatment of early rheumatoid arthritis and reduction of cardiac risk factor has greater impact on the course of the disease.
An Unusual Presentation of a Central Giant Cell Granuloma and Initial Treatment with Intralesional Steroids– A Case Report and Review of the Literature

A case of a 6 year-old boy is presented with an extensive intraoral central giant cell granuloma, which was initially thought to be a lesion of odontogenic origin. Central giant cell granuloma is an unusual lesion to be found within the oral cavity. Treatment ranges from radical surgical resection to conservative approaches, such as the one presented, with intralesional steroid injections. We would agree with previous work that this as a viable treatment adjunct and possible alternative to surgery for central giant cell granuloma of the jaws.
Protective Role of L-Carnitine and Tocopherol Against Cold Restraint Stress Induced Gastric Lesions In Streptozotocin–Diabetic Rats

In the present study, the influence of cold restraint stress (CRS)-induced gastric damage in diabetic rats, in relation to the antioxidative system was investigated. Male albino rats were used in the study, they were divided into 5 groups: i): non stressed group, ii): control CRS group, iii) diabetic CRS group (the rats of this group were injected with streptozotocin (STZ) 70 mg/kg i.p. and used 4 weeks after induction of diabetes with blood glucose levels of >350 mg/dl), iv): STZ L-carnitine pretreatment group (STZ-induced diabetic rat of this group were given L-carnitine 500 mg/kg 30 min before CRS) and v): STZ-vitamine E pretreatment group (STZ-induced diabetic rat of this group were given vitamin E 60 mg/kg body wt three weeks before CRS). The last four groups were exposed to CRS, at the end of each experiment, gastric damage was observed macroscopically. CRS induced gastric lesion, that was markedly exacerbated in STZ diabetic rats, but this aggravation was significantly suppressed by pretreatment with either L-carnitine or tocopherol (vitamin E) pretreatments. Diabetic rat stomachs showed significantly less glutathione peroxidase (GPX) activity as well as reduced glutathione (GSH) content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to CRS was significantly mitigated by decreasing lipid peroxidation by pretreatment with either L-carnitine or vitamin E. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to cold restraint–induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced GPX activity and GSH content. Based on these data, the beneficial effects of L-carnitine and vitamin E on CRS-induced mucosal injury especially in diabetics may be attributed to their antioxidative effects.
The Effect of Biologic Materials and Oral Steroids on Radiographic and Clinical Outcomes of Horizontal Alveolar Ridge Augmentation.

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone density when biologics were added (p-value=0.0653). No statistically significant difference found in the bone density with the addition of oral steroids. The use of tenting screws and resorbable occlusive membranes and a combination of allograft and xenograft bone materials provides significant clinical and radiographic dimensional changes in alveolar ridge width. THE EFFECT OF BIOLOGIC MATERIALS AND ORAL STEROIDS ON RADIOGRAPHIC AND CLINICAL OUTCOMES OF HORIZONTAL ALVEOLAR RIDGE AUGMENTATION. By: AMY REICHERT, DDS A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University. Virginia Commonwealth University, 2019 Thesis Advisor: JANINA GOLOB DEEB, DDS, MS DEPARTMENT OF PERIODONTICS Purpose: The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal ridge augmentations. Methods: A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 horizontal ridge augmentation patients. Information was gathered regarding surgical technique, grafting materials, post-operative healing, bone growth and bone density
Path planning on satellite images for unmanned surface vehicles

ABSTRACT In recent years, the development of autonomous surface vehicles has been a field of increasing research interest. There are two major areas in this field: control theory and path planning. This study focuses on path planning, and two objectives are discussed: path planning for Unmanned Surface Vehicles (USVs) and implementation of path planning in a real map. In this paper, satellite thermal images are converted into binary images which are used as the maps for the Finite Angle A* algorithm (FAA*), an advanced A* algorithm that is used to determine safer and suboptimal paths for USVs. To plan a collision-free path, the algorithm proposed in this article considers the dimensions of surface vehicles. Furthermore, the turning ability of a surface vehicle is also considered, and a constraint condition is introduced to improve the quality of the path planning algorithm, which makes the traveled path smoother. This study also shows a path planning experiment performed on a real satellite thermal image, and the path planning results can be used by an USV.
Testing properties of Ising models

Given samples from an unknown multivariate distribution p, is it possible to distinguish whether p is the product of its marginals versus p being ε-far from every product distribution? Similarly, is it possible to distinguish whether p equals a given distribution q versus p and q being ε-far from each other? These problems of testing independence and goodnessof-fit have received enormous attention in statistics, information theory, and theoretical computer science, with sample-optimal algorithms known in several interesting regimes of parameters [14, 15, 17, 18, 20]. Unfortunately, it has also been understood that these problems become intractable in large dimensions, necessitating exponential sample complexity. Motivated by the exponential lower bounds for general distributions as well as the ubiquity of Markov Random Fields (MRFs) in the modeling of high-dimensional distributions, we study distribution testing on structured multivariate distributions, and in particular the prototypical example of MRFs: the Ising Model. We demonstrate that, in this structured setting, we can avoid the curse of dimensionality, obtaining sample and time efficient testers for independence and goodness-of-fit which yield a sample complexity of poly(n)/ε2 on nnode Ising models. Along the way, we develop new tools for establishing concentration of functions of the Ising model, using the exchangeable pairs framework developed by Chatterjee [27], and improving upon this framework. In particular, we prove tighter concentration results for multi-linear functions of the Ising model in the high-temperature regime. We also prove a lower bound of n/ε on the sample complexity required for testing uniformity and independence of n-node Ising models. Thesis Supervisor: Constantinos Daskalakis Title: Associate Professor of Electrical Engineering and Computer Science
Can monocyte to HDL ratio be used as an inflammatory marker in children with familial mediterranean fever?

Aim: Familial Mediterranean fever (FMF); is an auto-inflammatory disease characterized by recurrent fever attacks. Inflammation continues even in the attack-free period. Monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is an inflammatory marker that has recently begun to use. The aim of the study was to evaluate the relationship between MHR and FMF in children. Material and Methods: Sixty-two children with FMF in the attack-free period and 60-age and sex-matched- healthy controls included in the study. Patients divided into subgroups according to their gene mutation type. Monocyte count and HDL-C levels retrieved from medical records of patients and MHR were calculated from these data. Results: The MHR of individuals were close to each other and there was no statistically significant difference between them ( p>0.05). Twenty-four of the patients had heterozygous, 4 had homozygous, 11 had a compound and 21 had negative mutations. Two of the patients had no mutation analysis. There was no significant difference between these four groups according to MHR (p=0.348). However, MHR revealed a positive correlation with fibrinogen (r=0.604, p
Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS

Objective To evaluate the combined effect of lesion activity and pathologic processes occurring in both chronically demyelinated lesions and normal-appearing white matter (NAWM) on brain atrophy in MS. Methods Pre- and post-gadolinium T1, fluid attenuation inversion recovery, and diffusion tensor imaging images were acquired from 50 consecutive patients with relapsing-remitting MS (all, but one, on disease-modifying therapy) at baseline and 5 years. Brain atrophy was measured using structural image evaluation, using normalization of atrophy percent brain volume change (PBVC) analysis. Results During follow-up, brain volume diminished by 2.0% ± 1.1%. PBVC was not associated with patient age, disease duration, sex, or type of treatment. PBVC moderately correlated with baseline lesion load (r = −0.38, p = 0.016), but demonstrated strong association with new lesion activity (r = −0.63, p < 0.001). Brain atrophy was also strongly linked to the increase of water diffusion within chronic MS lesions (r = −0.62, p < 0.001). In normal-appearing white matter (NAWM), PBVC demonstrated a significant correlation with both baseline and longitudinal increase of demyelination as measured by radial diffusivity (RD, r = −0.44, p = 0.005 and r = −0.35, p = 0.026, respectively). Linear regression analysis explained 62% of the variance in PBVC. It confirmed the major role of new lesion activity (p = 0.002, standardized beta-coefficient −0.42), whereas change in diffusivity inside chronic lesions and NAWM RD at baseline also contributed significantly (p = 0.04 and 0.02, standardized beta-coefficient −0.31 and −0.29, respectively), increasing predictive power of the model by 55%. Conclusion In addition to new lesion activity, progressive loss of demyelinated axons in chronic lesions and the degree of demyelination in NAWM significantly contribute to accelerated loss of brain tissue in patients with MS receiving immunomodulatory therapy.
Relationship between obesity, physical activity, sleeping hours and red blood cell parameters in adult Sudanese population

Ideal body weight with proper physical activity and good sleep are essential parameters for good quality of life. This study is concerned with assessing the association of general obesity, physical activity and sleeping hours with hemoglobin (Hb) concentration and red blood cell (RBC) parameters in healthy adults in Sudan. In this cross sectional study, 1086 healthy adults between 20 and 60 years were included out of which 275 were males and 811 were females. A complete blood count (CBC) was performed for Hb, RBC count, PCV, MCH and MCHC using Sysmex KX-21 automated hematology analyzer. The median and 95 percentile (2.5th to 97.5th) range values for Hb and RBC count in underweight were 13.0 (Range: 9.6-16.7) g/dl and 4.6 (Range: 3.6-5.8) ×1000/µL respectively, while Hb and RBC count in obese were 13.1 (Range: 10.4-17.0) g/dl and 4.6 (Range: 3.7-5.9) ×1000/µL respectively, with no significant difference. The RBC count (p=0.004) and Hb (p≤0.001) were significantly high in physically active compared to physically inactive participants; whereas the hemoglobin concentration (p=0.047), red blood cells (p=0.007) and hematocrit (p≤0.001) values were significantly low in long-term sleep compared to normal sleeping hours. In conclusion, there were no significant differences in hemoglobin concentration, RBC count, PCV, MCH and MCHC between under weight, normal weight, overweight and obese persons. Increased physical activity was associated with higher Hb levels and RBC counts, while long-term sleep showed lower Hb and RBCs.
Traditional Acupuncture Meets Modern Nanotechnology: Opportunities and Perspectives

Acupuncture is an ancient method in traditional Chinese medicine (TCM). Usually acupuncture needles are inserted into the body to achieve therapeutic effects. However, there are still some challenges to achieve consensuses. What is the essence or anatomy of acupuncture meridians? How does acupuncture work? How to improve acupuncture clinical therapeutic effect? These questions may be addressed by highlighting recent developments in innovative nanotechnology. The aim of this review is to elucidate the possible applications and future potential of nanotechnology in acupuncture. Nanoparticles are promising for imaging and it may gain a better understanding of the essence of meridian. Nanotechnology enables nanochips/nanosensors providing new solutions in detection reactive molecules in vivo and in real time. The connections and changing of these molecules with needle stimulation will allow insight into the mechanisms of acupuncture. Acupuncture combined with nano-TCM could provide a great potential in some type of characteristic acupuncture therapies improvement. By virtue of nanotechnology, the acupuncture needles could be innovated as multifunction toolbox. Acupuncture needles could be considered as a method for controlled drug delivery. The nanoparticulated photothermal, magnetothermal, photodynamic agents could also be filled on the surface of needle.
Towards Clinical Trials in Fuchs Endothelial Corneal Dystrophy: Classification and Outcome Measures—The Bowman Club Lecture 2019

The surgical treatment of Fuchs endothelial corneal dystrophy (FECD) has advanced dramatically over the last two decades. Penetrating keratoplasty has been superseded by various iterations of endothelial keratoplasty, and currently, surgical removal of host Descemet membrane without keratoplasty is being investigated. These surgical advances have been accompanied by significant improvement of our understanding of the underlying disease mechanisms, not least the discovery that FECD in western populations is predominantly an intronic trinucleotide repeat expansion disorder in the transcription factor 4 gene that results in RNA toxicity and mis-splicing. Understanding the disease mechanisms augurs well for developing targeted molecular medical therapies, which will require careful clinical investigation through trials to prove their efficacy and safety. As the field advances towards clinical trials, investigators should carefully define the disease state being treated and consider the options for outcome measures relevant to the type of intervention. FECD, and the outcomes of interventions to treat the disease, can be measured in terms of corneal morphology, corneal function and clinical impact. Standardising the approach for defining FECD and careful thought about the outcomes of intervention that are reported will help make the results of future trials for FECD applicable in clinical practice.
Functional analysis of RP2 and ARL3 in X-linked retinitis pigmentosa

iv Lay Summary . vi Abbreviations . vii . 9 . 9 Chapter 1: Introduction . 10 1.1 General Structure and Function of the Retina and Photoreceptor Cells . 10 1.1.1 Photoreceptor OS Morphogenesis . 12 1.1.2 OS Disc Shedding . 14 1.1.3 Photoreceptor Connecting Cilia . 15 1.1.4 Phototransduction . 16 1.1.5 Comparison of Human and Mouse Retina . 23 1.2 Inherited Retinal Degeneration . 24 1.2. 1 X-Linked Retinitis Pigmentosa . 26 1.2. 2 RPGR Function in the Photoreceptor . 27 1.2. 3 Mechanisms of Cell Death in RP . 28 1.3 RP2 and ARL3 Protein Structure and Function . 35 1.3. 1 The RP2 Protein . 35 1.3. 2 RP2 Pathogenic Mutations . 37 1.3. 3 RP2 vs RPGR Patient Phenotype . 37 1.3. 4 The ARL3 protein . 38 1.4 Roles of RP2 and ARL3 in Ciliary Trafficking . 40 1.4. 1 General Principles of Cilia . 40 1.4. 2 Intraflagellar Transport . 40 1.4. 3 Lipid Modified Protein Trafficking . 42 1.5 The Role of RP2 and ARL3 in Photoreceptor Protein Trafficking . 44 1.5. 1 Intraflagellar Transport in Photoreceptors . 44 1.5. 2 Trafficking of OS Proteins in Photoreceptors . 46