Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

BACKGROUND The Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) study was a retrospective analysis of 606 patients with unresectable colorectal liver metastases treated with radioembolization (RE) using 90Y-labeled resin microspheres. The first analysis of this study was completed with a last patient follow-up of 77.7 months. We now provide an updated survival analysis through September 15, 2016, with a last patient follow-up of 125 months. METHODS 90Y-RE was considered for patients with advanced liver-only or liver-dominant metastatic colorectal cancer which was deemed not suitable for surgery, ablation, or systemic therapy, and which had progressed or become refractory to at least one line of systemic therapy. All patients with a diagnosis of metastatic colorectal cancer who had received at least 1 RE treatment and 1 follow-up visit were included in the analysis. Patients were treated between July 2002 and December 2011 at one of 11 U.S. tertiary care centers. Data were collected at baseline, on the day of the first 90Y-RE treatment (day 0), and at all subsequent visits or until death. Patient medical charts and/or public records were accessed to obtain dates of death. RESULTS Dates of death were obtained for 574 out of a total of 606 patients, and overall survival (OS) data analyzed. Updated median OS was 10.0 months (95% CI: 9.2-11.8 months) at a median follow-up of 9.5 months versus the originally reported median OS of 9.6 months (95% CI: 9.0-11.1 months) at a follow-up of 8.6 months in the first MORE analysis. Patients received a median (range) of 2 (0 to 6) lines of chemotherapy. Baseline characteristics and factors significantly associated with patient survival (P<0.01) are consistent with those reported in the first safety analysis of the MORE study. These factors include poor ECOG performance status, markers of advanced disease such as increased extent of tumor-to-target liver involvement, poor baseline liver function, pre-treatment anemia, lung shunt fraction, and number of lines of prior chemotherapy. Patient age did not significantly affect survival outcomes. CONCLUSIONS Long-term follow-up confirms that 90Y-RE treatment offers favorable survival benefits for patients with unresectable metastatic colorectal cancer, even among patients who received 3 or more prior lines of chemotherapy. Our analysis also supports earlier reported prognostic factors for survival after 90Y-RE. Overall, our updated analysis confirms that 90Y-RE treatment provided a meaningful response and survival advantage for MORE patients across all ages and across diverse community and academic centers in the U.S.
Effects of Loperamide on Intestinal Ion Transport

The synthetic opiate loperamide (LPMD) is an antidiarrheal compound which affects both intestinal motility and the transport of water and electrolytes. We have investigated its effects on ion transport in the stripped ileal mucosa of rabbits, mounted in Ussing chambers in vitro. Addition of LPMD to serosal bathing medium resulted in a dose-dependent decrement of short-circuit current (Isc). LPMD (50 μM) significantly increased net Cl absorption (Jc1,) and JRnet (assumed to represent HCO3 secretion). LPMD also inhibited the Isc increments evoked either by agents that increase 3‘,5’-cyclic adenosine monophosphate (cAMP) content (theophylline and prostaglandin E2) or by the Ca2+ ionophore A23187; the opiate, however, did not prevent the Isc change induced by 3‘,5’-cyclic guanosine monophosphate (cGMP)-related agents such as 8-Br-cGMP and Escherichia coli heat-stable enterotoxin. LPMD did not alter basal or secretagogue-stimulated tissue cAMP. In contrast, LPMD caused a small increase in cGMP content of stripped ileal mucosa, but not in that of isolated entero-cytes. The role of Ca2+ in LPMD action is suggested by the significantly different effect of the drug on JCtnet in the presence and in the absence of Ca2+ in the serosal solution.
Cholecystokinin (CCK)‐expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK‐deficient mice

The suprachiasmatic nucleus (SCN) is the principal pacemaker driving circadian rhythms of physiology and behaviour. Neurons within the SCN express both classical and neuropeptide transmitters which regulate clock functions. Cholecyctokinin (CCK) is a potent neurotransmitter expressed in neurons of the mammalian SCN, but its role in circadian timing is not known. In the present study, CCK was demonstrated in a distinct population of neurons located in the shell region of the SCN and in a few cells in the core region. The CCK neurons did not express vasopressin or vasoactive intestinal peptide. However, CCK‐containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light‐responsive as evaluated by induction of cFOS, and did not express the core clock protein PER1. Accordingly, CCK‐deficient mice showed normal entrainment and had similar τ, light‐induced phase shift and negative masking behaviour as wild‐type animals. In conclusion, CCK signalling seems not to be involved directly in light‐induced resetting of the clock or in regulating core clock function. The expression of CCK in a subpopulation of neurons, which do not belonging to either the VIP or AVP cells but which have synaptic contacts to both cell types and reverse innervation of CCK neurons from VIP neurons, suggests that the CCK neurons may act in non‐photic regulation within the clock and/or, via CCK projections, mediate clock information to hypothalamic nuclei.
Stability and microbiological quality of rice bran subjected to different heat treatments

Rice bran is a byproduct commonly used for animal feeding; however its nutritional value and potential application in human diet have attracted market interest. Its preservation for safe use is still a challenge, so the objective of this study was to determine the quality of commercially available rice bran samples subjected to different heat treatments (extruding, parboiling, toasting, and microwave oven heating) in order to promote stabilization during storage under room temperature. Rice bran samples were collected from two industries, and each treatment was divided in three parts, each corresponding to three repetitions. All samples were evaluated for moisture content, total microorganisms, mold and yeast counting, hydrolytic rancidity, and lipase activity during 90 days of storage. Most of the heat treatments, including domestic and thermoplastic extrusion, generated products which may be used for human consumption under the tested conditions in terms of physicochemical and microbiological quality. The domestic treatments were more efficient in eliminating microorganisms or keeping them within acceptable limits. The toasted rice bran showed satisfactory results in terms of moisture, hydrolytic rancidity control, and lipase activity.
An educational program on depressive disorders for general practitioners on Gotland: background and evaluation

ABSTRACT General practitioners are the psychiatrists’ most important co‐workers in the treatment of depressive disorders. A high degree of knowledge about this illness in this group of doctors is of decisive importance. However, the value of postgraduate educational programs for general practitioners has been questioned. The Swedish Committee for the Prevention and Treatment of Depression (PTD) offered an educational program on symptoms, etiology, diagnosis, prevention and treatment of depression to all general practitioners on the Swedish island of Gotland. Lectures on suicide, depressive illness in childhood and in old age and psychotherapy of depressive states were also given. In several control periods data were collected on suicides, referrals to the local psychiatric department, emergency admissions, the quantity of sick leave used and the quantity of inpatient care due to depression. Even the prescription of psychopharmacological drugs on the island was investigated. Overall, the results indicated that general practitioners gratefully accepted the educational program and achieved increasing competence and stringency in treating and preventing depressive states. The program was associated with decreases in the use of psychiatric inpatient care and the sick leave frequency of depressed patients. The possibility of preventing suicides was positively influenced.
Angiographic characteristics of epileptogenic arteriovenous malformations and effectiveness in the seizure control after treatment with radiosurgery.

Objetive Define the angiographic characteristics of epileptogenic arteriovenous malformations (AVM) and assess symptom control of the seizure after treatment with radiosurgery. Material and Methods Between 1996 and 2006, a total of 237 adults patients were diagnosed with AVM and were treated in our center by radiosurgery with linear accelerator. We analyzed demographics, clinicals, angiographics and radiosurgicals characteristics and the complications of the procedure in each of them. The first symptom was a seizure in 68 of them and the subsequent analysis of the treatment effectiveness for the seizure control was done, and the possible predictive factors of AVM nidus evolution were assessed. Result The average volume of the epileptogenic AVMs was 7.17 cc, compared ot the non-epileptogenic AVM 5.06 cc (p<0.03). Other differentiating factors were surface blood supply (p<0.003), venous ectasia (p<0.064), angiogenesis (p<0.078), and the presence of unrelated aneurysms (p<0.08). For 68 patients (28.7%) with seizures a clinical control (Seizure Frequency Scoring System SFSS ≤2) was obtained in 70% of patients and there was an excellent control (SFSS ≤1) in 25% of them. The percent occlusion of their AVMs was 50%. There was statistical significance with SFSS ≤1 (p<0.01), but was not any significance with SFSS ≤2. Age (p<0.003) and diffuse nidus morphology (p<0.05) were predictors of good AVM nidus evolution. Conclusions The stereotactic radiosurgery seems to be an effective method for control of symptomatic seizures for intracranial AVMs. Certain angiographic characteristics, such as the volume, surface blood supply, angiogenesis, venous ectasia, and unrelated aneurysms to the AVMs, seem to influence the appearance of epileptic seizures.
Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells from inflammatory dental pulps via NF-κB pathway.

OBJECTIVE This study was designed to investigate the effects of mineral trioxide aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). MATERIALS AND METHODS inflammatory DPSCs were isolated from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned medium. MTT assay and flow cytometry were performed to evaluate the proliferation of iDPSCs. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time RT-PCR, and Western blot assay were used to investigate the differentiation capacity as well as the involvement of NF-κB pathway in iDPSCs. RESULTS Mineral trioxide aggregate-treated iDPSCs demonstrated the higher ALP activity and formed more mineralized nodules than the untreated group. The odonto/osteoblastic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP, respectively) in MTA-treated iDPSCs were significantly upregulated as compared with untreated iDPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in MTA-treated iDPSCs were significantly increased in a time-dependent manner. Moreover, the inhibition of NF-κB pathway suppressed the MTA-induced odonto/osteoblastic differentiation of iDPSCs, as indicated by decreased ALP levels, weakened mineralization capacity and downregulated levels of odonto/osteoblastic genes (Osx, Ocn, and Dspp). CONCLUSIONS Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway.
Anti-angiogenic therapies for advanced esophago-gastric cancer

Abstract Neo-vascularization is a vital process for tumor growth and development which involves the interaction between tumor cells and stromal endothelial cells through several growth factors and membranous receptors which ultimately activate pro-angiogenic intracellular signaling pathways. Inhibition of angiogenesis has become a standard treatment option for several tumor types including colorectal cancer, glioblastoma and ovarian cancer. In gastric cancer, the therapeutic role of anti-angiogenic agents is more controversial. Bevacizumab and ramucirumab, two monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, have been demonstrated antitumor activity in patients with tumors of the stomach or esophagogastric junction. However, especially for bevacizumab, this antitumor activity has not consistently translated into a survival advantage over standard treatment in randomized trials. In this article, we provide an overview of the role of angiogenesis in gastric cancer and discuss the results of clinical trials that investigated safety and effectiveness of antiangiogenic therapies in this disease. A review of the literature has been done using PubMed, ClinicalTrials.gov website and the ASCO Annual Meeting Library.
Therapeutic Strategies Targeting Cancer Stem Cells

The classical clonal evolution theory of neoplastic development supports the notion that cellular transformation results from random mutations and subsequent clonal selection. However, recent advancements in identification of the malignant populations responsible for tumor maintenance and recurrence have lent support to the cancer stem cell (CSC) hypothesis as a model of carcinogenesis, and posit that tumor growth is driven by a rare subpopulation of cells with stem cell-like properties. Cancer stem cells are commonly thought of as derivatives of a normal tissue stem cell that undergoes genetic alterations, which allow for sustained aggressive and clonal characteristics, self-renewal capacity and the ability to differentiate into all populations within a malignancy. Cancer stem cells alone, as compared to the bulk of cells in a tumor, are considered to be responsible for tumor initiation, metastasis and resistance to treatment. Moreover, CSCs are believed to share many properties with normal stem cells providing them with an overall insensitivity to conventional radioand chemotherapy. Therefore, successful targeting of such a highly tumorigenic yet rare population must be considered in order to improve the therapeutic efficacy of the currently available anti-cancer therapy. Here, we provide a summary of recent progress towards development of biomarkers that identify CSCs, the molecular mechanisms behind the conventional anti-cancer therapy resistance, and the development of therapeutic strategies to selectively target CSC populations.
Evaluation of airway complications in high-risk preterm infants: application of flexible fiberoptic airway endoscopy.

OBJECTIVES We sought to determine factors that would predict the development of subglottic stenosis (SGS) and tracheomalacia (TM) in preterm infants. The utility of a semiquantitative measurement of airway dimensions was assessed in relation to signs of airway complications. We also sought to determine from a high-risk population of infants those likely to have abnormal findings identified by bronchoscopic examination. METHODS Prospective airway endoscopy was performed for preterm infants who were intubated for 7 days or more or who demonstrated chronic oxygen needs beyond 28 days after birth and 36 weeks postconceptional age. Subjects were 117 preterm (less than 36 weeks' gestation) infants from two level III intensive care nurseries. Endoscopy was used to classify the type and degree of airway injury. Subglottic stenosis was defined subjectively and compared with an objective measurement using subglottic spatial relations described as a trans-subglottic/vocal cord ratio (TSG/VC). Clinical signs and symptoms and other risk factors were evaluated as significant predictors of SGS and TM, identified by bronchoscopy. RESULTS Moderate or severe airway abnormalities were identified in 32 patients (27.3%); 13 with SGS, 17 with TM, and 2 with both. All but one infant with TSG/VC less than 0.83 had signs and symptoms of airway dysfunction. Variables more commonly found in patients with SGS included greater number of intubations, use of inappropriately large endotracheal tubes, and longer duration of intubation. Higher averaged mean airway pressure during the first week after birth and lower gestational age were clinical features associated with TM. CONCLUSIONS Flexible bronchoscopic evaluation of a high-risk population demonstrated a higher incidence of moderate or severe SGS or TM than previously suspected. Subglottic stenosis and TM appear to have different etiologies based on different factors associated with their development. The TSG/VC ratio correlated well with obstructive symptoms and may represent a means to quantitate clinically subglottic narrowing. Infants with chronic lung disease who have persistently elevated partial pressure of carbon dioxide, apnea, or phonation abnormalities are most likely to have airway abnormalities identifiable by bronchoscopy.
Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men.

Effects of a 10-week progressive strength training program composed of a mixture of exercises for increasing muscle mass, maximal peak force, and explosive strength (rapid force production) were examined in 8 young (YM) (29+/-5 yrs) and 10 old (OM) (61+/-4 yrs) men. Electromyographic activity, maximal bilateral isometric peak force, and maximal rate of force development (RFD) of the knee extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF), muscle fiber proportion, and fiber areas of types I, IIa, IIb, and IIab of the vastus lateralis were evaluated. Maximal and explosive strength values remained unaltered in both groups during a 3-week control period with no training preceding the strength training. After the 10-week training period, maximal isometric peak force increased from 1311+/-123 N by 15.6% (p <.05) in YM and from 976+/-168 N by 16.5% (p <.01) in OM. The pretraining RFD values of 4049+/-791 N*s(-1) in YM and 2526+/-1197 N*s(-1) in OM remained unaltered. Both groups showed significant increases (p < .05) in the averaged maximum IEMGs of the vastus muscles. The CSA of the QF increased from 90.3+/-7.9 cm2 in YM by 12.2% (p <.05) and from 74.7+/-7.8 cm2 in OM by 8.5% (p <.001). No changes occurred in the muscle fiber distribution of type I during the training, whereas the proportion of subtype IIab increased from 2% to 6% (p < .05) in YM and that of type IIb decreased in both YM from 25% to 16% (p < .01) and in OM from 15% to 6% (p < .05). The mean fiber area of type I increased after the 10-week training in YM (p < .001) and OM (p < .05) as well as that of type IIa in both YM (p < .01) and OM (p < .01). The individual percentage values for type I fibers were inversely correlated with the individual changes recorded during the training in the muscle CSA of the QF (r=-.56, p < .05). The present results suggest that both neural adaptations and the capacity of the skeletal muscle to undergo training-induced hypertrophy even in older people explain the gains observed in maximal force in older men, while rapid force production capacity recorded during the isometric knee extension action remained unaltered during the present mixed strength training program.
Veterinary Forensic Pathology of Animal Sexual Abuse

Animal sexual abuse (ASA) involves harm inflicted on animals for the purposes of human sexual gratification and includes such terms as bestiality, zoophilia, zoosadism, animal sexual assault, and others. The prevalence of ASA is not known, although it may be more common than is currently perceived. Veterinarians have the skills required to identify and document cases of ASA. This article reviews the terminology, legal definitions and forms of ASA, and its social and psychological context. An investigative approach is outlined, including an alternate light source examination; collection of swabs for DNA analysis; sampling vaginal washes, rectal washes, and toenails for trace evidence and biologic analyses; radiographic studies; and a complete forensic necropsy, including histopathology. Gross lesions identified in ASA victims include injuries to the anus, rectum, penis, scrotum, nipples, and vagina; the presence of foreign bodies; and abrasions, bruising, and other evidence of nonaccidental injury. Specialized procedures, including examination using alternate light sources and screening tests to identify human seminal fluid within samples from ASA victims, are of potential value but have not been validated for use in animals.
Children's Development of Reaching: Temporal and Spatial Aspects of Aimed Whole-Arm Movements

Age-related changes in movement time and spatial distribution of pointing errors were investigated using a whole-arm target-aimed task. 60 children (6 to 11 yr.) and 10 young adults were required to reach towards targets located on a vertical screen in four conditions: target lit for 4 sec. in light (1), in darkness (2), target lit for 200 msec. in light (3), in darkness (4). Accuracy was perfect in Conditions 1 and 2, with a significant increase of MT in Condition 2 between the ages 7 and 10. Accuracy decreased slightly in Condition 3 and strongly in Condition 4, despite a similar shortening of MT. In Condition 4 the subjects undershot the target position: horizontally from age 8 and vertically in all age groups, with an increase of vertical bias by girls at age 9. These results suggest age-related changes in computation of arm movement towards the target.
Determination of pH

Показатель концентрации ионов водорода рН есть мера активности этих ионов в растворах. Зависимость громадного количества химических, биохимических, природных, технологических и многих других процессов от величины рН стимулирует развитие теории и техники измерения этого показателя. Рассмотрено современное состояние способов измерения рН. Трудно отыскать такую область науки, технологии и химии растворов, в которой не использовалась бы величина рН. Шкала рН была предложена датским химиком Зеренсеном. Изучая биохимические реакции, в частности гидролиз пепсина и усвоение протеинов в кислотно-солевых смесях, Зеренсен в 1909 году обнаружил их чрезвычайно сильную зависимость от изменения концентрации ионов водорода. Он нашел, что эффективная концентрация ионов водорода, непосредственно воздействующих на процесс, изменялась в широком диапазоне концентраций и часто оказывалась непривычно малой величиной. Для удобства Зеренсен предложил записывать ее в экспоненциальной форме = 10 − р = 1/10 р . Позднее символ − р был заменен обозначением рН. На современном языке р понимают как оператор р = − lg, таким образом, pH = − lg[H + ]. Именно так трактуется это обозначение в Номенклатурных правилах Международного союза по теоретической и прикладной химии (International Union for Pure and Applied Chemistry), ИЮПАК [1].