Miracle-dz/UniFAR-FTUs huggingface dataset:
Different Forms Effect of Single Complementary Metamaterial Structure on Square Patch Antenna

In this paper, we propose four different shapes square, circular, triangular, and rhombicof single complementary double negative metamaterial (C-DNM) structure incorporated into the square patch antenna. We compare the performance of the proposed structure with a conventional patch antenna, in a same parametric analysis with HFSS simulator. The operating frequency of this antenna is around 12 GHz for Xband applications. The parameters that considered in these works are resonant frequency, reflection coefficient, directivity, bandwidth and radiation pattern. The focusing parameter is to achieve the better directivity gain and directional radiation pattern that obtained from the single double negative C-DNM patch antenna. The simulations show that the addition of C-DNM to square patch antenna provides better performance in terms of directivity 7.78dB to 8.02dB for square metamaterial.
Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.
On the stability of sequences inserted into viral genomes

Abstract Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.
Cdx2 Animal Models Reveal Developmental Origins of Cancers

The Cdx2 homeobox gene is important in assigning positional identity during the finely orchestrated process of embryogenesis. In adults, regenerative responses to tissues damage can require a replay of these same developmental pathways. Errors in reassigning positional identity during regeneration can cause metaplasias—normal tissue arising in an abnormal location—and this in turn, is a well-recognized cancer risk factor. In animal models, a gain of Cdx2 function can elicit a posterior shift in tissue identity, modeling intestinal-type metaplasias of the esophagus (Barrett’s esophagus) and stomach. Conversely, loss of Cdx2 function can elicit an anterior shift in tissue identity, inducing serrated-type lesions expressing gastric markers in the colon. These metaplasias are major risk factors for the later development of esophageal, stomach and colon cancer. Leukemia, another cancer in which Cdx2 is ectopically expressed, may have mechanistic parallels with epithelial cancers in terms of stress-induced reprogramming. This review will address how animal models have refined our understanding of the role of Cdx2 in these common human cancers.
Therapeutic Class Overview Insulin and Combination Agents

Page 1 of 23 This information is considered confidential and proprietary to OptumRx. It is intended for internal use only and should be disseminated only to authorized recipients. The contents of the therapeutic class overviews on this website ("Content") are for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Clinicians should refer to the full prescribing information and published resources when making medical decisions. Therapeutic Class Overview Insulin and Combination Agents
1. LA FASE DIAGNOSTICA

La presenza di alcuni fattori porta ad aumentato rischio di carcinoma del colon-retto. L' eta e sicuramente il parametro che influenza maggiormente il rischio di malattia, infatti 1'incidenza ecirca 10 volte superiore nella classe di eta compresa tra 60-64 anni rispetto a quella 40-44 anni. Alcune malattie infiammatorie cronic he quali la colite ulcerosa, e pin recentemente sembra anche la malattia di Crohn, costituiscono un fattore di rischio. Per quanto riguarda la colite ulcerosa il rischio di sviluppare un carcinoma del colon-retto edi circa il 3% a 20 anni, il 7% a 30 anni ed il 20% a 40 anni. Nella malattia di Crohn einvece segnalato un rischio variabile da 7 a 20 volte piu elevato rispetto alla popolazione generale (Benhattar J. et al., 1995). L'anamnesi di un adenoma del colon-retto e un altro accertato fattore di rischio. Fattori di rischio dietetici sono stati riportati in numerosi studio II consumo di elevate quantita di grassi ed una assunzione ridotta di fibre vegetali sono associati ad una aumentata incidenza di carcinoma del colon-retto (Fernandez et al., 1996). Esiste poi una predisposizione genetica al cancro del colon-retto. II ruolo della ereditarieta e piu evidente nelle poliposi adenomatose ereditarie (poliposi familiare, sindrome di Turcot, sindrome di Gardner) che sono trasmesse con modalita autosomica dominante e comportano, se non viene attuata una colectomia precoce, 10 sviluppo di un cancro del colon-retto in quasi tutti i soggetti. II cancro ereditario non associato a poliposi 0 sindrome di Lynch rappresenta una situazione caratterizzata da una elevata incidenza di carcinomi del colonretto in assenza di una estesa poliposi, in una eta compresa tra i 40 e i 50 anni. I polipi sono presenti rna non sono numerosi come nella poliposi familiare, sono piccoli, piani e situati prevalentemente nel colon destro: questi tumori rappresentano il 5% circa di tutti i tumori del colon-retto (Kinzler, 1996). PREVENZIONE
Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding

Significance Chronic kidney disease (CKD) remains a major health concern worldwide, affecting ∼10% of the population. Previous genome-wide association studies have identified many genes associated with CKD, but conclusive demonstrations of their roles in kidney function remain largely unexplored. Here, we identify the mechanistic basis of one such gene by creating mice deficient for Galnt11. We demonstrate that Galnt11 influences kidney function by site-specific modification of the endocytosis receptor megalin within the proximal tubules of the kidney. Loss of Galnt11 results in reduced megalin-mediated ligand binding and an age-related reduction in megalin levels, resulting in low-molecular-weight proteinuria. Our results identify a factor required for proper kidney function and provide insight into its association with CKD. Chronic kidney disease (CKD) affects more than 20 million Americans and ∼10% of the population worldwide. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of 1 GWAS-identified gene by creating mice deficient for Galnt11, which encodes a member of the enzyme family that initiates protein O-glycosylation, an essential posttranslational modification known to influence protein function and stability. We find that Galnt11-deficient mice display low-molecular-weight proteinuria and have specific defects in proximal tubule-mediated resorption of vitamin D binding protein, α1-microglobulin, and retinol binding protein. Moreover, we identify the endocytic receptor megalin (LRP2) as a direct target of Galnt11 in vivo. Megalin in Galnt11-deficient mice displays reduced ligand binding and undergoes age-related loss within the kidney. Differential mass spectrometry revealed specific sites of Galnt11-mediated glycosylation within mouse kidney megalin/LRP2 that are known to be involved in ligand binding, suggesting that O-glycosylation directly influences the ability to bind ligands. In support of this, recombinant megalin containing these sites displayed reduced albumin binding in cells deficient for Galnt11. Our results provide insight into the association between GALNT11 and CKD, and identify a role for Galnt11 in proper kidney function.
Vaginal Myomectomy for Prolapsed Submucous Fibroid: It is Not Only  About Size

Leiomyoma of the uterus, also called fibroids, are common in women. In this case report, we describe the case of a nulliparous woman with a large, prolapsed submucous uterine leiomyoma of 10 × 11 cm was vaginally impacted. The aim is to highlight the challenges in managing such uncommon clinical scenario focusing on the factors predicting the success of vaginal myomectomy including the size of the myoma but also the role of vaginal laxity to allow the steps of devascularization, detachment, and removal of the myoma. We also describe the preoperative and intraoperative methods that can be used to minimize intraoperative blood loss and enhance the safety and feasibility of the surgical procedure. Gonadotropin therapy was not applicable in our patient, and other treatments were also unavailable such as temporary ligation of uterine arteries, while others were unsuccessful like devascularization by hysteroscopy, twisting, and ligation of the pedicle. The final resort used in our case was morcellation of the myoma with intact pedicle, which should be attempted by experienced gynecologic surgeons only.
Epidemiology of Pediatric Tracheostomy and Risk Factors for Poor Outcomes: An 11-Year Single-Center Experience

Objective Children with long-term tracheostomies are at higher risk of complications. This study aims to describe the epidemiology, outcomes, and factors associated with successful decannulation in children undergoing tracheostomy. Study Design Case series with chart review. Setting Tertiary hospital. Subjects and Methods A retrospective analysis was conducted on pediatric tracheostomies performed from 2006 to 2016. Demographics, preexisting comorbidities, indications for tracheostomy, and pretracheostomy ventilatory requirements were collected. A multivariate regression model with covariates of age, failure to thrive (FTT), and comorbidities was used to identify factors associated with successful decannulation. Secondary outcomes were ventilation and oxygen requirements at hospital discharge, hospital and intensive care unit length of stay, and complications. Results In total, 105 patients received a tracheostomy at a median age of 8.0 months (interquartile range, 2.0-45.0). The most common indication was anatomic airway obstruction (55 of 105, 52.5%). Forty-four (41.9%) patients had preexisting FTT. In-hospital mortality was 14 of 105 (13.3%). None were directly related to tracheostomy. At discharge, 40 of 91 (44.0%) and 12 of 91 (13.2%) required home mechanical ventilation and supplemental oxygen, respectively. Forty-one (39%) patients underwent successful decannulation at a median 408 days (interquartile range, 170-1153) posttracheostomy. On adjusted analysis, unsuccessful decannulation was more common in patients with FTT and neurologic comorbidities. Postoperative complications were more common in younger patients and those with a longer time to decannulation. Conclusion Neurologic comorbidities and FTT were risk factors for unsuccessful decannulation after pediatric tracheostomy. Nutritional interventions may have a role in improving long-term outcomes following pediatric tracheostomies and should be investigated in future studies.
Monoclonal antibody pharmacogenomics in cancer treatment

Conventionally, in the pharmacokinetic/pharmacodynamic analysis of small molecule compounds such as cytotoxic anticancer drugs, polymorphism analysis of genes related to absorption, distribution, metabolism, and excretion has been performed in addition to the analyses of blood concentrations of drugs. Such pharmacogenetic factors play an important role in predicting therapeutic effects and adverse events and in the proper use of drugs. With the recent launch of immune checkpoint inhibitors (ICIs) and the rapid development of antibody-drug conjugates (ADCs) currently underway, there is no doubt that antibody drugs, which are large molecule compounds, will become key drugs in anticancer drug treatment. However, the pharmacokinetic and pharmacodynamic analysis of antibody drugs is still not sufficient, and further elucidation of factors and mechanisms affecting their dynamics in the human body is necessary. Moreover, the pharmacogenomic factors of antibody drugs have not yet been fully studied. There are many factors that should be clarified, such as factors that regulate the host immune response in ICI therapy and the effects of ATP-binding cassette transporter and cytochrome P450 on the payload of ADCs. This review provides an outline of antibody drugs in cancer treatment and summarizes the pharmacogenomic factors of antibody drugs known to date.
Molecular profiling of radical prostatectomy tissue from patients with no sign of progression identifies ERG as the strongest independent predictor of recurrence

Background: As a major cause of morbidity and mortality among men, prostate cancer is a heterogenous disease, with a vast heterogeneity in the biology of the disease and in clinical outcome. While it often runs an indolent course, local progression or metastasis may eventually develop, even among patients considered “low risk” at diagnosis. Therefore, biomarkers that can discriminate aggressive from indolent disease at an early stage would greatly benefit patients. We hypothesized that tissue specimens from early stage prostate cancers may harbor predictive signatures for disease progression. Methods: We used a cohort of radical prostatectomy patients with longitudinal follow-up, who had tumors with low grade and stage that revealed no signs of future disease progression at surgery. During the follow-up period, some patients either remained indolent (non-BCR) or progressed to biochemical recurrence (BCR). Total RNA was extracted from tumor, and adjacent normal epithelium of formalin-fixed-paraffin-embedded (FFPE) specimens. Differential gene expression in tumors, and in tumor versus normal tissues between BCR and non-BCR patients were analyzed by NanoString using a customized CodeSet of 151 probes. Results: After controlling for false discovery rates, we identified a panel of eight genes (ERG, GGT1, HDAC1, KLK2, MYO6, PLA2G7, BICD1 and CACNAID) that distinguished BCR from non-BCR patients. We found a clear association of ERG expression with non-BCR, which was further corroborated by quantitative RT-PCR and immunohistochemistry assays. Conclusions: Our results identified ERG as the strongest predictor for BCR and showed that potential prognostic prostate cancer biomarkers can be identified from FFPE tumor specimens.
Tumour Regression via Integrative Regulation of Neurological, Inflammatory, and Hypoxic Tumour Microenvironment

Changing trends in anticancer research have altered the treatment paradigm to the extent that it is difficult to investigate any anticancer drugs without mentioning immunotherapy. Thus, we are finally contemplating tumour regression using magic bullets known as immunotherapy drugs. This review explores the possible options and pitfalls in tumour regression by first elucidating the features of cancer and the importance of tumour microenvironments. Next, we evaluated the trends of anticancer therapeutics regulating tumour microenvironment. Finally, we introduced the concept of tumour regression and various targets of tumour microenvironment, which can be used in combination with current immunotherapy for tumour regression. In particular, we emphasize the importance of regulating the neurological manifestations of tumour microenvironment (N) in addition to inflammation (I) and hypoxia (H) in cancer.
Identifying and Overcoming Barriers to Resident Use of Point-of-Care Ultrasound

Introduction Emergency medicine residency programs have rigorous point-of-care ultrasound (POCUS) curricula. However, this training does not always readily translate to routine use in clinical decision-making. This study sought to identify and overcome barriers that could prevent resident physicians from performing POCUS during clinical shifts. Methods This was a two-step process improvement study. First, a survey was deployed to all residents of a three-year academic residency program to identify barriers to clinical use of POCUS. This survey identified the perceived lack of a uniform documenting protocol as the most important barrier to performing POCUS on shift. Second, as an intervention to overcome this barrier, a streamlined documentation protocol was developed and presented to residents. The primary outcome was the number of patients who had POCUS used in medical decision-making one year before and after intervention. Secondary outcomes were the level of training of residents performing exams and whether faculty overseeing exams were trained through an ultrasound fellowship program. Results POCUS use by residents increased from 82 to 223 patients before and after the intervention, respectively. Per resident, this translates to an absolute increase from 2.2 (95% confidence intervall [CI], 1.4, 3) to 5.8 (95% CI, 4, 7.6) or 3.6 (95% CI, 1.8, 5.4) exams/resident over the study period. We observed no significant difference in the proportions of scans attributable to the resident level of training (χ2 = 0.5, p = 0.47). The proportion of exams by non-ultrasound fellowship trained faculty increased significantly more compared to fellowship trained faculty (χ2 = 19, p<0.0001); however, both ultrasound fellowship trained and non-ultrasound fellowship trained faculty increased the absolute number of exams performed. Conclusion A key perceived barrier to resident-performed POCUS is unfamiliarity with documenting ultrasounds for medical decision-making. Educating residents in person about a POCUS documentation protocol may help overcome this barrier. Incorporating resident input and motivation into POCUS incentivization may increase utilization. Future studies in optimizing POCUS on shift will need to focus on streamlining documentation, addressing time constraints, and faculty support for resident-performed POCUS.
NDT_A_214595 2015..2025

Fatma Dilara Altunbas Baris Onen Unsalver Alisan Burak Yasar 1Uskudar University, Department of Psychology, Istanbul, Turkey; 2Marmara University Hospital, Department of Psychiatry, Istanbul, Turkey Objective: This study investigated Theory of Mind (ToM) abilities as measured by a hinting task and the Reading the Mind in the Eyes Test (RMET) in individuals diagnosed with posttraumatic strees disorder (PTSD) in relation to different types of childhood trauma and compared to a healthy control group. Method: RMET, a Clinician Administered PTSD Scale (CAPS), a Beck Depression Inventory (BDI), a Childhood Trauma Questionnaire (CTQ), a hinting task, and a socio-demographic questionnaire were administered to PTSD (n=30) patients and healthy controls (n=30). Results: There was a significant difference in ToM performance between healthy participants and the PTSD group (p<0.001). A significant correlation was found between trauma types and ToM performance (p<0.01). The diagnosis of PTSD and the severity of PTSD symptoms showed significant correlations with ToM performance (p<0.01). In comparison with the healthy control group, the PTSD group demonstrated lower performance on both ToM tasks. Regardless of the PTSD diagnosis, those people who had a history of childhood trauma had slowed reaction times in response to photographs representing emotionally salient mental states and demonstrated difficulties in the identification of irony/hints in the context of the administered assessment task. Conclusion: The findings of the present study suggest that a diagnosis of PTSD and a history of different types of trauma have an effect on ToM performance. PTSD seems to lead to deterioration in ToM capacities. This may mean that the experience of childhood adversity may lead to long-lasting damage to social cognition. The current study is helpful in that it contributes to a better understanding of the pathogenesis of PTSD; moreover, it will be beneficial in the development of new treatment options. Our research findings suggest that we must concentrate not only on traumatic events during the treatment process of PTSD follow-up and treatment; we must also target deficiencies in cognitive and emotional capabilities.