Miracle-dz/UniFAR-FTUs huggingface dataset:
KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.

PURPOSE Adding targeted therapies to chemotherapy in metastatic colorectal cancer (CRC) improves response rates and survival. KRAS is a predictive indicator for anti-epidermal growth factor receptor (EGFR) treatments. The most important reasons for KRAS discordance are intratumoral heterogeneity and incorrect mutation analysis. Evaluating the status of KRAS in primary and metastatic lesions becomes even more crucial to ensure efficient usage of anti-EGFR treatments. METHODS Patients with metastatic CRC, whose primary disease and liver and/or lung metastases were operated, were retrospectively evaluated, and KRAS assessment was performed on 31 patients who were suitable for DNA analysis. Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis. RESULTS The median age of 31 patients diagnosed with rectal cancer (N=13) and colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was detected in 22% (7/31) of the patients. While 3 patients with detected discordance had mutated KRAS in the primary material, wild type KRAS was detected in their liver or lung lesions. On the other hand, while 4 patients had wild type KRAS in the primary material, mutated KRAS was determined in their liver or lung lesions. The McNemar test revealed no significant discordance between primary and metastatic disease (p=1.00). No progression free survival (PFS) difference was detected between patients with determined discordance and patients with undetermined discordance (10.6 vs 14.7 months, p=0.719). CONCLUSION This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data. In the literature and recent studies with large patient numbers in which modern KRAS tests were used, the KRAS discordance rate varies between 3-12%. In our study, a higher KRAS discordance (22%) was detected, and no survival difference was determined between patients with or without discordance. In recent years, the rising interest in borderline resectable disease may bring forward discussions related to which material the KRAS status should be analyzed.
Cardiac Transplantation in the New Era

The prevalence of heart failure continues to rise due to the aging population and longer survival of people with conditions that lead to heart failure, eg, hypertension, diabetes, and coronary artery disease. Although medical therapy has had an important impact on survival of patients and improving quality of life, heart transplantation remains the definitive therapy for patients that eventually deteriorate. Since the first successful heart transplantation in 1967, significant improvements have been made regarding donor and recipient selection, surgical techniques, and postoperative care. However, the number of potential organ donors has not changed and the growing number of patients in need for transplantation has resulted an increase in waiting list time, and the need for mechanical support. To overcome this issue, the United Network for Organ Sharing implemented an allocation system to prioritize the sickest patients on the list to receive organs. Despite the careful selection of patients, pretransplant immunological screening, and multidrug immunosuppressive regimens, acute and chronic rejections occur and potentially limit graft and patient survival. Treatment for rejection largely depends on the type of rejection, the presence of hemodynamic compromise, and time after transplantation. The limiting factor for long-term graft survival is allograft vasculopathy, an immune-mediated process causing diffuse narrowing of the coronary arteries. Percutaneous coronary intervention and coronary artery bypass surgery are often not an option for this vasculopathy due to the lack of focal lesions, and retransplantation is the only option in appropriate patients.
Investigation on the performance of a compact microstrip monopulse antenna array

A microstrip monopulse antenna array has been designed and manufactured. The array, the monopulse comparator and the feed network are placed on the same layer resulting in a very compact structure. But the compact structure may bring some limitations to the improvement of the array performance. In this paper, several factors that affect the array performance are investigated which may serve as the guideline of the design. The -16 dB side lobe level for the sum pattern and 25 dB null depth for the difference pattern have been achieved in the experiment. The simulation and the analysis show that there is still a possibility to improve the array performance.
Management of rhinosinusitis: an evidence based approach

Purpose of reviewThe most recent recommendations for the management of both acute (ARS) and chronic rhinosinusitis (CRS) based on the strongest data available for each treatment modality are summarized in this review. The clinical relationships between CRS and its comorbidities are also discussed. Recent findingsThe most promising advances in rhinosinusitis management involve the use of mAbs (anti-IgE, anti-IL-5, anti-IL-4R&agr;) in trials of CRS with nasal polyposis. Otherwise, the mainstays of treatment for both ARS and CRS have largely remained the same over the past several years. SummaryThe treatment of ARS primarily involves symptomatic control with intranasal corticosteroids and nasal saline irrigation; antibiotics should be reserved for the patients who are believed to have bacterial rhinosinusitis. Treating CRS effectively involves using intranasal corticosteroids and irrigation, systemic corticosteroids, and potentially systemic antibiotics. Biologics (mAbs) have shown benefit in clinical studies. Providers should also be aware of concomitant disease processes that may afflict patients with CRS.
Post-hepatectomy Refractory Ascites in Cirrhotic Patients with Hepatocellular Carcinoma: Risk Factor Analysis to Overcome this Problematic Complication.

BACKGROUND Refractory ascites is a serious post-hepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy. PATIENTS AND METHODS The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites. RESULTS Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor. CONCLUSION Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for post-hepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication.
Coexpression of herpesviral thymidine kinase reporter gene and VEGF gene for noninvasive monitoring of therapeutic gene transfer: an in vitro evaluation.

UNLABELLED Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). METHODS Accumulation of 14C-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FIAU) and 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (FHBG) as reporter probes, and secretion of VEGF into medium, were determined for Ad4tk-infected H9c2 rat cardiac cells in vitro. RESULTS In vitro tracer uptake increased with increasing vector concentration and over time. It was comparable to cells infected with adenovirus expressing only wild-type HSV1-tk (reporter probe: 14C-FIAU) or mutant HSV1-sr39tk (reporter probe: 18F-FHBG). No significant uptake was observed in cells infected with adenovirus expressing VEGF alone. With increasing vector concentration, Ad4tk-infected cells increasingly released VEGF into medium. VEGF production correlated significantly with cellular reporter probe uptake (r = 0.93; P = 0.0003). CONCLUSION The usefulness of a vector coexpressing HSV1-tk and VEGF for noninvasive imaging of expression of a therapeutic transgene has been demonstrated in vitro. This approach may allow for future in vivo monitoring of cardiac angiogenesis gene therapy.
Evolutionary multi-objective optimization of H∞ controller for inductive power transfer system

Aiming at achieving robust control of an Inductive Power Transfer (IPT) system and based on an H∞ loop-shaping algorithm, this paper proposes a multi-objective optimization framework to ensure an optimal performance. Three objectives and constraints related to the H∞ loop-shaping design and singular structured value are defined to optimize the robust stability and robust performance. A time-domain objective, that is Integral of Time-weighted Squared Error (ITSE), is presented to achieve optimal transient response with low overshoot and zero steady-state error. Then an evolutionary multi-objective algorithm is presented as a computational method to search for a set of non-dominated H∞ loop-shaping controllers automatically. Experimental results verify the optimality of the designed method.
Is yoga an effective treatment in the management of patients with chronic low back pain compared with other care modalities – a systematic review

Abstract Objective: The aim of the study was to assess randomized-control trials (RCTs) to ascertain whether yoga is an effective treatment in the management of patients with chronic low back pain (cLBP) compared with other care modalities. Methods: A search strategy was formulated with key concepts identified using the PICO process. Four databases were searched in June 2012. Appropriate eligibility criteria were set and implemented. Results: Four randomized control trials met the inclusion criteria. All four papers found that yoga lead to a significant improvement in back function, and three demonstrated a significant improvement in back pain when compared with certain care modalities. All papers had significant limitations identified, however. Conclusions: Given the limitations identified within the studies, the conclusions drawn must be considered conservatively. Although early results appear promising, but further well-designed RCTs are warranted, with multiple, specified comparator care modalities before firm conclusions can be gained.
Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression

Recent studies showed that a polymorphism (T to C nucleotide substitution) in the 3′ flanking region of the human CLOCK gene is associated with diurnal preferences of human healthy subjects, with higher “eveningness” in subjects carrying at least one copy of the C allele. We investigated the possible role of CLOCK gene polymorphism in the regulation of diurnal mood fluctuations during a major depressive episode. Sample (n = 101) was collected, in the context of previously reported trials, among patients affected by bipolar disorder type I, depressive episode without psychotic features, free of psychotropic medications. Perceived mood levels were assessed three times a day with self‐administered visual analogue scales. Genotype groups showed no significant difference in diurnal mood fluctuations. When stratifying the sample by including only patients with an adequate period of observation (duration of illness higher than 5 years, n = 69), we post‐hoc observed a significantly higher recurrence rate in homozygotes for the C variant, which was almost double than that of the other genotype groups. This preliminary observation leads to hypothesize a role for the CLOCK gene polymorphism in the regulation of long‐term illness recurrence in bipolar disorder. Given the post‐hoc nature of the finding, replication in independent samples is necessary to confirm it. © 2003 Wiley‐Liss, Inc.
Feeding trial in pigs with a diet containing sodium n-butyrate.

Pigs weighing 7 to 102 kg were fed a diet containing 0.17% sodium n-butyrate. The diet increased the average daily body mass gain of pigs by 23.5%. Due to its dietetic effect, feed consumption increased by 8.9%. However, owing to the higher feed conversion, specific feed utilization was reduced by 11.8%. The experimental diet markedly reduced the percentile proportion of coliform bacteria in the ileum as compared to Lactobacillus ssp. : it decreased the coliform count and increased the counts of Lactobacillus spp. The diet increased the length of ileal microvilli and the depth of caecal crypts. It raised the concentration of immunoreactive insulin in the blood plasma. The feed supplemented with sodium butyrate did not alter adversely the clinical indices tested. It reduced feed costs by 9% and increased the returns from sales by 13%. As the additive is normally produced by microbial fermentation in the large intestine, it is not alien to the body. Sodium butyrate exerted its favourable effect in 3.6- to 24.2-fold lower concentrations than the organic acids (citric acid, fumaric acid, propionic acid) used earlier. With respect to its favourable biological and economic effect, sodium n-butyrate can be recommended for use in pig feeding as a growth promoter.
The Involvement of Neural Retina Pax6 in Lens Fiber Differentiation

Proper eye formation depends on specific interactions between neural and ectodermal tissues coupled with temporally distinct gene expression and a regulated sequence of signaling events. The homeobox gene Pax6 is vitally important to the entire process of eye development in both vertebrates and invertebrates. Pax6 expression for the retina anlage has been shown to be indispensable in the development of various retinal cells. Here, we report that Pax6 expression in neural tissue plays an important role in lens development. Expression of a dominant-negative version of Pax6 isoform that lacks 5a-exon sequence in developing optic vesicles (OV) of chick embryos led to arrest of lens development at the lens vesicle stage as well as optic cup deformation. To gain insights into the molecular events underlying deformed lens formation, we examined the expression of several transcription factors in the lens of Pax6-negative-OV eye. Importantly, L-Maf was downregulated while c-Maf was found normal in deformed lens. We detected a downregulation of fibroblast growth factor (FGF8) in the neural tissue. Our in vivo experiments suggest that Pax6 in neural retina regulates FGF8 expression, which may maintain L-Maf expression in the lens to be essential for later lens fiber differentiation.
What can be learned from patient stories about living with the chronicity of heart illness? A narrative inquiry

Background: Patients’ illness stories are valuable information that supports person-centred care across the illness trajectory. Aims: To learn how older South Asian immigrant women experience living with heart illness long after discharge from hospital. Method: We used narrative inquiry, a personal experience method that explores and interprets lived and told stories through the three dimensions of experience. Design: Four participants, over the age of sixty, living with heart illness for over ten years, were invited to engage in narrative interview and Narrative Reflective Process. Outcomes: Giving patients voice, allows caregivers insight into the human experience of illness beyond hospitalization. Considering the increased migration of people around the globe, this knowledge is significant in provision of person-centred care. Implications: Person-centred care does not end with the hospitalization and outpatient clinics. Inter-disciplinary teams need to reconsider the trajectory of chronic illnesses and the care required throughout, especially for marginalized populations.
Microscopic colitis - a missed diagnosis in diarrhea-predominant irritable bowel syndrome.

BACKGROUND Clinical presentation in microscopic colitis (MC) is similar in many cases to that of diarrhea-predominent irritable bowel syndrome (IBS-D). The proper differential diagnosis requires total colonoscopy with multiple biopsies from normal-appearing mucosa and a detailed histopathological exam. Specific treatment may improve symptomatology. AIM To evaluate the prevalence of MC in patients with an initial diagnosis of IBS-D, to analyse demographic and clinical features of MC patients and to assess the efficacy of specific treatment. MATERIAL AND METHODS Our retrospective study analyzed patients diagnosed with microscopic colitis in clinic during a three-year period. Diagnosis was established on histological exams of the samples obtained during colonoscopy in patients previously thought to have IBS-D. We evaluated clinical manifestations, time lapsed from their onset to definitive diagnosis, the association of MC with autoimmune diseases or with prior medication and the efficacy of treatment with budesonide or mesalazine. RESULTS From 247 patients considered to have IBS-D, 15 patients (6.07%) had actually MC (13 lymphocytic colitis and 2 collagenous colitis). MC was associated with nonsteroidal antiinflammatory drugs (3 patients), Lansoprazole (2 patients) and autoimmune diseases (6 patients). Watery, non-bloody diarrhea was present in all patients with MC. Other frequent complaints were nocturnal diarrhea (11 patients), abdominal pain (8 patients), abdominal bloating and flatulence (8 patients) and slight weight loss (6 patients). The diagnostic samples were obtained from the right colon in 6 cases and from rectosigmoid or transverse colon in 9 patients. Treatment was initial symptomatic in all patients, but there were 5 patients that required mesalazine and/or Budesonide, with favourable outcome. CONCLUSIONS All the patients thought to have diarrhea-irritable bowel syndrome should be evaluated for microscopic colitis. Symptomatology is almost superimposable, but a few distinct features can be noticed. The proper and early diagnosis and the specific treatment may lead to significant clinical improvement in some difficult cases of the so-called "irritable bowel syndrome".
Full factorial screening of human embryonic stem cell maintenance with multiplexed microbioreactor arrays

Use of human pluripotent stem cells (hPSCs) in regenerative medicine applications relies on control of cell fate decisions by exogenous factors. This control can be hindered by the use of undefined culture components, poorly understood autocrine/paracrine effects, spatiotemporal variations in microenvironmental composition inherent to static culture formats, and signal cross‐talk between multiple factors. We recently described microbioreactor arrays that provide a full factorial spectrum of exogenous factors, and allow gradual accumulation of paracrine factors through serial culture chambers. We combined these with defined biochemical conditions, and in situ reporter gene‐ and immunofluorescence‐based readouts to create an hPSC screening platform with enhanced data throughput and microenvironmental control. HES3‐EOS‐C(3+)‐EiP reporter hESCs were screened against FGF‐2, TGF‐β1, and retinoic acid in a modified mTeSR‐1 medium background. Differential pluripotency marker expression reflected mTeSR‐1's maintenance capacity, and differentiation in response to removal of maintenance factors or addition of retinoic acid. Interestingly, pluripotency marker expression was downregulated progressively through serial chambers. Since downstream chambers are exposed to greater levels of paracrine factors under continuous flow, this effect is thought to result from secreted factors that negatively influence pluripotency. The microbioreactor array platform decodes factor interplay, and has a broad application in deciphering microenvironmental control of cell fate.
Assessment of Neutrophil Gelatinase-associated Lipocalin in the Brain-dead Organ Donor to Predict Immediate Graft Function in Kidney Recipients: A Prospective, Multicenter Study

Background:Delayed graft function is a major determinant of long-term renal allograft survival. Despite considerable efforts to improve donor selection and matching, incidence of delayed graft function remains close to 25%. As neutrophil gelatinase-associated lipocalin (NGAL) has been shown to predict acute renal failure, the authors tested the hypothesis that NGAL measurement in brain-dead donors predicts delayed graft function in kidney recipients. Methods:In a prospective, multicenter, observational study, serum NGAL was measured in donors at the time of transfer to operating room. The primary endpoint was the delayed graft function, defined as the need for renal replacement therapy during the first week posttransplantation. Results:Among 159 included brain-dead donors, 146 were analyzable leading to 243 renal transplantations. Of these, 56 (23%) needed renal replacement therapy. Donors’ NGAL values were similar in case of both delayed and normal graft function in recipients. The area under the receiver-operating curve for NGAL to predict the need for renal replacement therapy before day 8 was 0.50 (95% CI, 0.42 to 0.59). The area under curve for NGAL to predict failure to return to a normal graft function at day 8 was 0.51 (95% CI, 0.44 to 0.59). Using multivariate analysis, NGAL was not associated to the need for renal replacement therapy (odds ratio, 0.99; 95% CI, 0.98 to1.00) or failure to return to a normal graft function at day 8 (odds ratio, 1.00; 95% CI, 0.99 to 1.00). Conclusion:NGAL measurement in brain-dead donors at the time of recovery failed to predict delayed or normal graft function in kidney recipients.
Transgenic Reexpression of GLUT1 or GLUT2 in Pancreatic β Cells Rescues GLUT2-null Mice from Early Death and Restores Normal Glucose-stimulated Insulin Secretion*

GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse α to β cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic β cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of α to β cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in β cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.