Miracle-dz/UniFAR-FTUs huggingface dataset:
En bloc resection of primary sacral tumors: classification of surgical approaches and outcome.

OBJECT En bloc resection with adequate margins is associated with the highest probability of long-term tumor control or cure in most cases of primary sacral malignancies. The authors present their experience with a systematic approach to these lesions. They provide a novel classification of surgical techniques based on the level of nerve root sacrifice and evaluate the functional and oncological outcomes. METHODS Seventy-eight consecutive patients underwent 94 resections of sacral neoplasms at The University of Texas M. D. Anderson Cancer Center in Houston between August 1993 and June 2002. The records of 29 consecutive patients who underwent en bloc resection of primary sacral tumors were retrospectively reviewed. The median follow-up period was 55 months (range 1-103 months). Chordoma was the most frequent tumor type (16 cases). Midline sacral amputation was performed in 25 patients (eight low, four middle, seven high, and five total sacrectomies; one hemicorporectomy). Lateral sacrectomy was undertaken in four patients (two unilateral excisions of the sacroiliac joint and two hemisacrectomies). The surgical margins were wide in 19 cases, marginal in nine, and contaminated in one. The type of sacrectomy correlated with characteristic outcomes with respect to bladder, bowel, and ambulatory functions. Duration of hospital stay was related to the extent of sacrectomy (p = 0.003, Wilcoxon signed-rank test). The median Kaplan-Meier disease-free survival for patients with chordoma was 68 months (95% confidence interval 46-90 months). CONCLUSIONS Classification of en bloc sacral resection techniques by the level of nerve root transection is useful in predicting postoperative function and the potential for morbidity. Adequate surgical margins should not be compromised to preserve function when they are necessary to affect tumor control.
Exploiting natural anti-tumor immunity for metastatic renal cell carcinoma

Clinical observations of spontaneous disease regression in some renal cell carcinoma (RCC) patients implicate a role for tumor immunity in controlling this disease. Puzzling, however, are findings that high levels of tumor infiltrating lymphocytes (TIL) are common to RCC. Despite expression of activation markers by TILs, functional impairment of innate and adaptive immune cells has been consistently demonstrated contributing to the failure of the immune system to control RCC. Immunotherapy can overcome the immunosuppressive effects of the tumor and provide an opportunity for long-term disease free survival. Unfortunately, complete response rates remain sub-optimal indicating the effectiveness of immunotherapy remains limited by tumor-specific factors and/or cell types that inhibit antitumor immune responses. Here we discuss immunotherapies and the function of multiple immune system components to achieve an effective response. Understanding these complex interactions is essential to rationally develop novel therapies capable of renewing the immune system's ability to respond to these tumors.
Dose and Timing of N‐Cadherin Mimetic Peptides Regulate MSC Chondrogenesis within Hydrogels

The transmembrane glycoprotein N‐cadherin (NCad) mediates cell–cell interactions found during mesenchymal condensation and chondrogenesis. Here, NCad‐derived peptides (i.e., HAV) are incorporated into hyaluronic acid (HA) hydrogels with encapsulated mesenchymal stem cells (MSCs). Since the dose and timing of NCad signaling are dynamic, HAV peptide presentation is tuned via alterations in peptide concentration and incorporation of an ADAM10‐cleavable domain between the hydrogel and the HAV motif, respectively. HA hydrogels functionalized with HAV result in dose‐dependent increases in early chondrogenesis of encapsulated MSCs and resultant cartilage matrix production. For example, type II collagen and glycosaminoglycan production increase ≈9‐ and 2‐fold with the highest dose of HAV (i.e., 2 × 10−3m), respectively, when compared to unmodified hydrogels, while incorporation of an efficient ADAM10‐cleavable domain between the HAV peptide and hydrogel abolishes increases in chondrogenesis and matrix production. Treatment with a small‐molecule ADAM10 inhibitor restores the functional effect of the HAV peptide, indicating that timing and duration of HAV peptide presentation is crucial for robust chondrogenesis. This study demonstrates a nuanced approach to the biofunctionalization of hydrogels to better emulate the complex cell microenvironment during embryogenesis toward stem‐cell‐based cartilage production.
C Terminus-mediated Control of Voltage and cAMP Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels*

The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of “pacemaker” channels includes 4 isoforms, the kinetics and cAMP-induced modulation of which differ quantitatively. Because HCN isoforms are highly homologous in the central region, but diverge more substantially in the N and C termini, we asked whether these latter regions could contribute to the determination of channel properties. To this aim, we analyzed activation/deactivation kinetics and the response to cAMP of heterologously expressed isoforms mHCN1 and rbHCN4 and verified that mHCN1 has much faster kinetics and lower cAMP sensitivity than rbHCN4. We then constructed rbHCN4 chimeras by replacing either the N or the C terminus, or both, with the analogous domains from mHCN1. We found that: 1) replacement of the N terminus (chimera N1–4) did not substantially modify either the kinetics or cAMP dependence of wild-type channels; 2) replacement of the C terminus, on the contrary, resulted in a chimeric channel (4-C1), the kinetics of which were strongly accelerated compared with rbHCN4, and that was fully insensitive to cAMP; 3) replacement of both N and C termini led to the same results as replacement of the C terminus alone. These results indicate that the C terminus of rbHCN4 contributes to the regulation of voltage- and cAMP-dependent channel gating, possibly through interaction with other intracellular regions not belonging to the N terminus.
Potential value of the common vetch (Vicia sativa L.) as an animal feedstuff: a review

The objective of this review was to systematically evaluate common vetch seeds as a potential feedstuff for animals, by summarizing and discussing the available published literature covering their nutritional composition as well as their content of antinutritional factors and potential techniques for their reduction. In addition, animal feeding studies that have investigated the effect of inclusion of common vetch seeds on animal growth and performance were identified and evaluated to stimulate interest in their use as a good source of nutrients for inclusion in animal diets. The collective literature shows that common vetch seeds are a less costly (in comparison with alternatives) and rich source of protein and minerals for farmed animals, are of high digestibility and have a high energy content, and can be used to partially or totally replace soya bean meal and/or to replace a large proportion of cereals in the diet. Furthermore, the literature shows that common vetch seeds contain a range of antinutritional factors which, if they are to be utilized in non-ruminant diets and to increase their utilizing efficiency, need to be removed or inactivated. This can be achieved via certain pre-processing methods, the combination of which may deliver better results.
Secondary Resource Allocation for Opportunistic Spectrum Sharing with IR-HARQ based Primary Users

We propose to address the problem of a secondary resource allocation when a primary Incremental Redundancy Hybrid Automatic Repeat reQuest (IR-HARQ) protocol. The Secondary Users (SUs) intend to use their knowledge of the IR-HARQ protocol to maximize their long-term throughput under a constraint of minimal Primary Users (PUs) throughput. The ACcumulated Mutual Information (ACMI), required to model the primary IR-HARQ protocol, is used to define a Constrained Markov Decision Process (CMDP). The SUs resource allocation is then shown to be a solution of this CMDP. The allocation problem is then considered as an infinite dimensional space linear programming. Solving the dual of this linear programming is similar to solving an unconstrained MDP. A solution is finally given using the Relative Value Iteration (RVI) algorithm.
Contradictory effects of β1- and α1- aderenergic receptor blockers on cardio-ankle vascular stiffness index (CAVI)--CAVI independent of blood pressure.

AIM The cardio-ankle vascular stiffness index (CAVI) is a new parameter that reflects the stiffness of the aorta, femoral artery and tibial artery as a whole. One of its conspicuous features is that CAVI is independent of blood pressure at measuring time, theoretically. But, it has not been experimentally proved yet. For confirmation, pharmacological studies were performed comparing with brachial-ankle pulse wave velocity (baPWV). METHODS Used drugs were a β1-adrenoceptor blocker, metoprorol and an α1- adrenoceptor blocker doxazosin. Both were administered to 12 healthy volunteer men. CAVI and baPWV were measured every one hour for 6 hours using VaSera. RESULTS When metoprolol (80 mg) was administered to 12 healthy volunteer men, systolic blood pressure decreased from 131.4 ± 4.5 to 118.3 ± 4.1 mmHg (mean ± SE) (p < 0.05) at the 3rd hour, and diastolic blood pressure decreased from 85.3 ± 4.0 to 75.3 ± 3.0 mm Hg (p < 0.05). baP-WV decreased from 13.93 ± 0.46 to 12.46 ± 0.49 m/sec (p < 0.05), significantly, but CAVI did not change (8.16 ± 0.29 to 8.24 ± 0.27) (p = 0.449). ΔbaPWV at each time was significantly correlated with both Δsystolic and Δdiastolic blood pressures, but ΔCAVI was not correlated with either Δblood pressure. When doxazosin (4 mg) was administered to the same men, systolic blood pressure decreased from 130.2 ± 4.6 to 117.2 ± 4.8 mmHg (p < 0.05) at the 3rd hour. Diastolic blood pressure also decreased from 85.1 ± 4.1 to 74.2 ± 3.9 mmHg (p < 0.05). baPWV decreased from 13.98 ± 0.68 to 12.25 ± 0.53 m/sec (p < 0.05), significantly. CAVI also decreased from 8.15 ± 0.28 to 7.18 ± 0.37 (p < 0.05), significantly. CONCLUSION These results suggested that CAVI was not affected by blood pressure at the measuring time directly, but affected by the changes of contractility of smooth muscle cells.
Clinical Predictors of Chemotherapy-Induced Nausea and Vomiting in Breast Cancer Patients Receiving Adjuvant Doxorubicin and Cyclophosphamide

Background: Patients with breast cancer often receive emetogenic anthracycline–based chemotherapy as part of their treatment. Chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as one of the distressing adverse effects among patients with cancer. Despite the advent of newer antiemetics and better understanding of the CINV pathophysiology, total eradication of CINV has yet to be achieved. Objective: To assess the incidence of nausea and vomiting in patients who have breast cancer and are receiving adjuvant doxorubicin and cyclophosphamide (AC) bolus chemotherapy, ascertain patients’ risk factors affecting CINV response, and study patient adherence to delayed antiemetics. Methods: This was a single-institution, prospective, observational study conducted at an outpatient cancer center in Singapore from December 2006 to December 2007. Clinical events such as CINV were collated using a standardized diary. Use of rescue antiemetics and unscheduled clinic visits due to CINV were documented. Results: Of a total of 108 participants, 16 patients were lost to follow-up and 1 provided incomplete information; thus, 91 patients were included in the analysis. Delayed antiemetics were given according to the institution's guideline and only 9 (9.9%) patients received aprepitant. Neither acute nor delayed vomiting was reported by a majority of patients and only 4 (4.4%) experienced grade 3 vomiting. The incidence of severe nausea was highest on day 3 of chemotherapy and affected 14.3% of patients. Anxiety and history of chemotherapy-induced nausea were associated with both acute and delayed nausea, and history of motion sickness was associated with delayed vomiting. Approximately 65% of patients were adherent to their prescribed delayed antiemetics. Conclusions: Most of our patients adhered to their antiemetics and tolerated AC chemotherapy reasonably well, without vomiting; yet nausea persisted. To improve CINV control, clinicians must actively communicate with patients to facilitate accurate assessment of risk factors and CINV response and to encourage adherence to delayed antiemetics.
Onset of epiphyseal mineralization and growth plate closure in radiographically normal and dysplastic Labrador retrievers.

OBJECTIVE To determine whether onset of mineralization of the femoral and proximal tibial epiphyses and age at closure of the femoral and acetabular triradiate growth plates was different for Labrador Retrievers that were radiographically normal or that had canine hip dysplasia (CHD). DESIGN Cohort study. ANIMALS 36 Labrador Retriever puppies. PROCEDURE Puppies were radiographed every other day from the time they were 8 to 10 days old until ossification of the femoral heads was apparent. Radiographs were then obtained weekly until puppies were 1 month old and then monthly until puppies were 8 to 12 months old. Age at which mineralization was first observed in the proximal and distal femoral and proximal tibial epiphyses and at which the femoral capital, triradiate acetabular, and distal femoral growth plates were no longer radiographically visible were recorded. Fifteen dogs were euthanatized and necropsied to determine whether dogs had CHD. RESULTS There were 26 radiographically normal left and right hip joints and 10 dysplastic left and right hip joints. Onset of mineralization of the proximal femoral epiphyses and of the right proximal tibial epiphysis was significantly later in dysplastic than in radiographically normal puppies. The left femoral capital growth plates closed significantly later in dysplastic than in radiographically normal joints, but other differences in growth plate closure were not detected. CLINICAL IMPLICATIONS Endochondral ossification may be abnormal in dogs with CHD. The disease appears to affect multiple joints, even though it is most evident clinically in the hip joint.
A Hybrid Discontinuous Galerkin Method for Elliptic Problems

A new family of hybrid discontinuous Galerkin methods is studied for second-order elliptic equations. Our proposed method is a generalization of the cell boundary element (CBE) method [Y. Jeon and E. -J. Park, Appl. Numer. Math., 58 (2008), pp. 800-814], which allows high order polynomial approximations. Our method can be viewed as a hybridizable discontinuous Galerkin method [B. Cockburn, J. Gopalakrishnan, and R. Lazarov, SIAM J. Numer. Anal. , 47 (2009), pp. 1319-1365] using a Bauman-Oden-type local solver. The method conserves the mass in each element and the average flux is continuous across the interelement boundary for even-degree polynomial approximations. Optimal order error estimates measured in the energy norm are proved. Numerical examples are presented to show the performance of the method.
AUTOINDUCTION OF MKC-963 [(R)-1-(1-CYCLOHEXYLETHYLAMINO)-4-PHENYLPHTHALAZINE] METABOLISM IN HEALTHY VOLUNTEERS AND ITS RETROSPECTIVE EVALUATION USING PRIMARY HUMAN HEPATOCYTES AND CDNA-EXPRESSED ENZYMES

MKC-963, (R)-1-(1-cyclohexylethylamino)-4-phenylphthalazine, a potent inhibitor of platelet aggregation, was synthesized and used in clinical trials in the 1990s. In the process of clinical study, it was found that urinary excretion ratios for 6β-hydroxycortisol and free cortisol increased significantly in parallel with decreases in the plasma concentrations of MKC-963 after repeated oral administration of the compound to healthy volunteers. These findings suggested that MKC-963 caused autoinduction (defined as the ability of a drug to induce enzymes that enhance its own metabolism, resulting in dispositional tolerance) in humans, and clinical studies using the compound were stopped. This experience prompted us to reevaluate the effects of this compound on CYP3A4 using primary human hepatocytes and cDNA-expressed human cytochrome P450 (P450) enzymes to determine whether the autoinduction of MKC-963 metabolism in humans could have been predicted if these in vitro systems had been used for the evaluation of MKC-963 in the preclinical study. The results of in vitro study showed that MKC-963 increased CYP3A4 mRNA expression level and activity of testosterone 6β-hydroxylation to extents similar to those observed with rifampicin in primary human hepatocytes. In addition, approximately 90% of the MKC-963 metabolism in human liver microsomes was estimated to be attributable to CYP3A4. These in vitro findings are in good agreement with the results of clinical study, suggesting that studies using human hepatocytes and cDNA-expressed human P450s are useful for assessing the autoinductive nature of compounds under development before starting clinical studies.
Hostility and Recovery from Melancholia

Twenty inpatients suffering from major depressive illness with melancholia were administered the hostility subscale of the Kellner Symptom Questionnaire and Paykel's Clinical Interview for Depression before and after treatment with amitriptyline. A matched control group of normal subjects had the same assessments at two points in time. Hostility decreased and friendliness increased in depressives after amitriptyline; upon recovery, there were no significant differences in hostility between depressed patients and control subjects, whereas such differences were striking during the illness. Patients who had reported losses before onset of illness rated themselves as more friendly than the other depressives; their hostility did not significantly decrease with recovery. The results suggest that hostility improves with the treatment of depression; life events appear to influence the degree of hostility in depressive illness as well as the response to treatment.
Evaluation of native entomopathogenic nematodes for the control of the European cherry fruit fly Rhagoletis cerasi L. (Diptera: Tephritidae) larvae in soil

Turkey is the world's largest producer of sweet cherries. The European cherry fruit fly, Rhagoletis cerasi L. (Diptera: Tephritidae), is a major pest of sweet cherry crops in Europe and Turkey. The detection of only one larva in the fruit by the processor can result in the rejection of the entire crop of that orchard and/or farm as \"wormy\" and unmarketable. The main control tactic for R. cerasi is to prevent the females from laying eggs in the fruit. Currently, only a few insecticides are being used, and their application is debatable due to problems with residual ecotoxicity for humans and beneficial organisms. As an alternative to using insecticides for the reduction of adult populations, 4 indigenous entomopathogenic nematode species, Steinernema carpocapsae (Anamur isolate), S. feltiae (Rize isolate), Heterorhabditis bacteriophora (Ekecik isolate), and H. marelatus (Ankara isolate), were bioassayed against last-instar R. cerasi larvae at different temperatures (10, 15, and 25 °C) and nematode concentrations (0, 100, 500, and 1000 IJs/larva). Temperature and nematode concentration had a significant effect on the efficacy of nematode species. S. feltiae was the most virulent species at all temperatures and nematode concentrations. Only S. feltiae showed higher than 40% mortality at low temperatures (10 and 15 °C). At 25 °C, S. feltiae caused 95% mortality, followed by H. marelatus (82%) and H. bacteriophora (76%), at 1000 IJs/larva concentration. Our results indicate that R. cerasi larvae are highly susceptible to entomopathogenic nematode infection. In particular, S. feltiae has high potential for reducing last-instar larval populations, thus decreasing the adult population in the spring.
Explaining Disability Trends in the U.S. Elderly and Near-Elderly Population.

OBJECTIVE To examine disability trends among U.S. near-elderly and elderly persons and explain observed trends. DATA SOURCE 1996-2010 waves of the Health and Retirement Study. STUDY DESIGN We first examined trends in Activities of Daily Living and Instrumental Activities of Daily Living limitations, and large muscle, mobility, gross motor, and fine motor indexes. Then we used decomposition analysis to estimate contributions of changes in sociodemographic composition, self-reported chronic disease prevalence and health behaviors, and changes in disabling effects of these factors to disability changes between 1996 and 2010. PRINCIPAL FINDINGS Disability generally increased or was unchanged. Increased trends were more apparent for near-elderly than elderly persons. Sociodemographic shifts tended to reduce disability, but their favorable effects were largely offset by increased self-reported chronic disease prevalence. Changes in smoking and heavy drinking prevalence had relatively minor effects on disability trends. Increased obesity rates generated sizable effects on lower-body functioning changes. Disabling effects of self-reported chronic diseases often declined, and educational attainment became a stronger influence in preventing disability. CONCLUSIONS Such unfavorable trends as increased chronic disease prevalence and higher obesity rates offset or outweighed the favorable effects with the result that disability remained unchanged or increased.