Miracle-dz/UniFAR-FTUs huggingface dataset:
Commissioning of MRI‐only based treatment planning procedure for external beam radiotherapy of prostate

In radiotherapy, target tissues are defined best on MR images due to their superior soft tissue contrast. Computed tomography imaging is geometrically accurate and it is needed for dose calculation and generation of reference images for treatment localization. Co‐registration errors between MR and computed tomography images can be eliminated using magnetic resonance imaging‐only based treatment planning. Use of ionizing radiation can be avoided which is especially important in adaptive treatments requiring several re‐scans. We commissioned magnetic resonance imaging‐only based procedure for external radiotherapy, treatment planning of the prostate cancer. Geometrical issues relevant in radiotherapy, were investigated including quality assurance testing of the scanner, evaluation of the displacement of skin contour and radiosensitive rectum wall, and detection of intraprostatic fiducial gold seed markers used for treatment localization. Quantitative analysis was carried out for 30 randomly chosen patients. Systematic geometrical errors were within 2.2 mm. The gold seed markers were correctly identified for 29 out of the 30 patients. Positions of the seed midpoints were consistent within 1.3 mm in magnetic resonance imaging and computed tomography. Positional error of rectal anterior wall due to susceptibility effect was minimal. Geometrical accuracy of the investigated equipment and procedure was sufficient for magnetic resonance imaging‐only based radiotherapy, treatment planning of the prostate cancer including treatment virtual simulation. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Timing of bolus in children with type 1 diabetes using continuous subcutaneous insulin infusion (TiBoDi Study).

BACKGROUND Continuous subcutaneous insulin infusion is considered a safe and effective way to administer insulin in pediatric patients with type 1 diabetes, but achieving satisfactory and stable glycemic control is difficult. Several factors contribute to control, including fine-tuning the basal infusion rate and bolus timing. We evaluated the most effective timing of a pump-delivered, preprandial bolus in children with type 1 diabetes. METHODS We assessed the response of 30 children with type 1 diabetes to a standard meal after different timing of a bolus dose. RESULTS The glucose levels for 3 h after the meal were lower (i.e., closer to the therapeutic target of <140 mg/dL) when the bolus doses were administered 15 min or immediately before the meal, rather than after the meal. However, these differences were not statistically significant, except at the 1-h postprandial time point: bolus just after meal, 177 +/- 71 mg/dL (9.83 +/- 3.94 mmol/L); 15 min before meal, 136 +/- 52 mg/dL (7.55 +/- 2.89 mmol/L) (P = 0.044); and just before meal, 130 +/- 54 mg/dL (7.22 +/- 3.00 mmol/L) (P = 0.024). The area under the curve (AUC) (in mg/min) did not differ significantly with different bolus times, but the SD of the AUC was the lowest with the bolus given 15 min before the meal. CONCLUSIONS These data support injection of the bolus before, rather than after, eating, even if the patient is hypoglycemic before meals.
Identification of a CD8 T Cell That Can Independently Mediate Autoimmune Diabetes Development in the Complete Absence of CD4 T Cell Helper Functions1

Previous work has indicated that an important component for the initiation of autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse model entails MHC class I-restricted CD8 T cell responses against pancreatic β cell Ags. However, unless previously activated in vitro, such CD8 T cells have previously been thought to require helper functions provided by MHC class II-restricted CD4 T cells to exert their full diabetogenic effects. In this study, we show that IDDM development is greatly accelerated in a stock of NOD mice expressing TCR transgenes derived from a MHC class I-restricted CD8 T cell clone (designated AI4) previously found to contribute to the earliest preclinical stages of pancreatic β cell destruction. Importantly, these TCR transgenic NOD mice (designated NOD.AI4αβ Tg) continued to develop IDDM at a greatly accelerated rate when residual CD4 helper T cells were eliminated by introduction of the scid mutation or a functionally inactivated CD4 allele. In a previously described stock of NOD mice expressing TCR transgenes derived from another MHC class I-restricted β cell autoreactive T cell clone, IDDM development was retarded by elimination of residual CD4 T cells. Hence, there is variability in the helper dependence of CD8 T cells contributing to the development of autoimmune IDDM. The AI4 clonotype represents the first CD8 T cell with a demonstrated ability to progress from a naive to functionally activated state and rapidly mediate autoimmune IDDM development in the complete absence of CD4 T cell helper functions.
Alpha-linolenic acid metabolism in men and women: nutritional and biological implications.

PURPOSE OF REVIEW This review critically evaluates current knowledge of alpha-linolenic acid metabolism in adult humans based on the findings of studies using stable isotope tracers and on increased dietary alpha-linolenic acid intake. The relative roles of alpha-linolenic acid and of longer-chain polyunsaturated fatty acids in cell structure and function are discussed together with an overview of the major metabolic fates of alpha-linolenic acid. The extent of partitioning towards beta-oxidation and carbon recycling in humans is described. The use and limitations of stable isotope tracers to estimate alpha-linolenic acid desaturation and elongation are discussed. A consensus view of the extent of alpha-linolenic acid conversion to longer-chain fatty acids in humans is presented. The extent to which increasing dietary alpha-linolenic acid intake alters the concentrations of longer-chain n-3 fatty acids is described. The biological and nutritional implications of these findings are discussed. RECENT FINDINGS Conversion of alpha-linolenic acid to eicosapentaenoic acid is limited in men and further transformation to docosahexaenoic acid is very low. A lower proportion of alpha-linolenic acid is used as a substrate for beta-oxidation in women compared with men, while the fractional conversion to longer-chain fatty acids is greater, possibly due to the regulatory effects of oestrogen. SUMMARY Overall, alpha-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate alpha-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.
Sensory processing and classroom emotional, behavioral, and educational outcomes in children with autism spectrum disorder.

OBJECTIVE We explored the associations between sensory processing and classroom emotional, behavioral, and educational outcomes of children with autism spectrum disorder (ASD). METHOD Twenty-eight children with ASD (with average-range IQ) were compared with 51 age- and gender-matched typically developing peers on sensory processing and educational outcomes. RESULTS For children with ASD, the Short Sensory Profile scores Underresponsive/Seeks Sensation and Auditory Filtering explained 47% of the variance in academic performance, yet estimated intelligence was not a significant predictor of academic performance. Significant negative correlations were found between (1) auditory filtering and inattention to cognitive tasks, (2) tactile hypersensitivity and hyperactivity and inattention, and (3) movement sensitivity and oppositional behavior. CONCLUSION A pattern of auditory filtering difficulties, sensory underresponsiveness, and sensory seeking was associated with academic underachievement in the children with ASD. Children who have difficulty processing verbal instructions in noisy environments and who often focus on sensory-seeking behaviors appear more likely to underachieve academically.
Evaluation of delayed puberty: what diagnostic tests should be performed in the seemingly otherwise well adolescent?

Delayed puberty (DP) is defined as the lack of pubertal development by an age that is 2–2.5 SDs beyond the population mean. Although it generally represents a normal variant in pubertal timing, concern that DP could be the initial presentation of a serious underlying disorder has led to a diagnostic approach that is variable and may include tests that are unnecessary and costly. In this review, we examine available literature regarding the recommended diagnostic tests and aetiologies identified during the evaluation of youth with DP. We view this literature through the prism of the seemingly otherwise well adolescent. To provide further clinical context, we also evaluate the clinical and laboratory data from patients seen with DP in our centre over a 2-year period. The literature and our data reveal wide variability in the number of tests performed and raise the question of whether tests, other than gonadotropins, obtained in the absence of signs or symptoms of an underlying disorder are routinely warranted. Together this information provides a pragmatic rationale for revisiting recommendations calling for broad testing during the initial diagnostic evaluation of an otherwise healthy adolescent with DP. We highlight the need for further research comparing the utility of broader screening with a more streamlined approach, such as limiting initial testing to gonadotropins and a bone age, which, while not diagnostic, is often useful for height prediction, followed by close clinical monitoring. If future research supports a more streamlined approach to DP, then much unnecessary testing could be eliminated.
Overview of Flaxseed Patent Applications for the Reduction of Cholesterol Levels.

BACKGROUND Flaxseed is becoming an increasingly widely used food ingredient. The rising interest of the food industry in this nutraceutical is primarily because of functional nutrients, such as alpha-linolenic acid and lignans, which have health benefits due to their lipid-lowering properties. OBJECTIVE The objective of this study was to provide an overview of the patenting of flaxseed products with cholesterol-lowering effects. METHOD Patent applications filed by country of origin were retrieved from the Derwent Innovations Index®database. RESULTS A total of 307 patent documents were identified, of which 184 claim the use of flaxseed or parts of the flax plant in the product formulation, for their lipid-lowering effect when consumed by humans. A few of the patent applications contain claims for new products based on flaxseed in isolation, including the preparation of foods designed to inhibit the production of cholesterol. Most of the claims were for flaxseed in the form of oil and in association with other lipid-lowering compounds, mainly for the food industry, in the form of dietary supplements or baked products designed to raise their high-density lipoprotein content, and for treating heart problems. China and the United States are the leading countries of flax-related applications. CONCLUSION These results may have important implications for the production of functional food products that meet specific societal demands.
Spatio-Temporal Analysis of Passenger Travel Patterns in Massive Smart Card Data

Metro systems have become one of the most important public transit services in cities. It is important to understand individual metro passengers’ spatio-temporal travel patterns. More specifically, for a specific passenger: what are the temporal patterns? what are the spatial patterns? is there any relationship between the temporal and spatial patterns? are the passenger’s travel patterns normal or special? Answering all these questions can help to improve metro services, such as evacuation policy making and marketing. Given a set of massive smart card data over a long period, how to effectively and systematically identify and understand the travel patterns of individual passengers in terms of space and time is a very challenging task. This paper proposes an effective data-mining procedure to better understand the travel patterns of individual metro passengers in Shenzhen, a modern and big city in China. First, we investigate the travel patterns in individual level and devise the method to retrieve them based on raw smart card transaction data, then use statistical-based and unsupervised clustering-based methods, to understand the hidden regularities and anomalies of the travel patterns. From a statistical-based point of view, we look into the passenger travel distribution patterns and find out the abnormal passengers based on the empirical knowledge. From unsupervised clustering point of view, we classify passengers in terms of the similarity of their travel patterns. To interpret the group behaviors, we also employ the bus transaction data. Moreover, the abnormal passengers are detected based on the clustering results. At last, we provide case studies and findings to demonstrate the effectiveness of the proposed scheme.
Effect of soy on faecal dry matter content and excretion of Brachyspira hyodysenteriae in pigs

The aim of this study was to investigate the effect of a soy diet on the excretion of Brachyspira hyodysenteriae in five farms with subclinically infected pigs. The effects on general health, faecal consistency and dry matter were analysed. In total, 200 pigs of different ages (group 1 <100 days of age (n=120) and group 2 ≥100 days (n=80)) were randomly assigned to the control (C) and the treatment (T) groups. Group C received the farm's standard diet. In group T half of the daily feed ration was replaced by pure soy on two consecutive days. Faecal scores were used to determine faecal consistency and a microwave method to assess faecal dry matter content (FDMC). In age group 1, soy feeding resulted in a statistically significant decrease of the FDMC of 2.5 per cent compared with group C and in age group 2 in a significant increase of 2.2 per cent compared with group C at day 2. Overall seven (T: 5, C: 2) out of 597 faecal samples tested positive for B hyodysenteriae by PCR. In conclusion, a high soy diet applied over two days influenced the faecal consistency and the FDMC in growers, finishers and sows under field conditions. Further investigations with more sensitive diagnostic methods are needed to prove a potential influence of a high soy diet on the detection rate of B hyodysenteriae in subclinically infected herds.
Insights into the Roles of Desolvation and π‐Electron Interactions during DNA Polymerization

This report describes the use of several isosteric non‐natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π‐electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high‐ and low‐fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high‐fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low‐fidelity HIV‐1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non‐natural nucleotides that are capable of hydrogen‐bonding or π‐stacking interactions. Surprisingly, hydrophobic analogues that function as efficient substrates for the E. coli Klenow fragment behave as noncompetitive or uncompetitive inhibitors against HIV‐1 reverse transcriptase. In these cases, the mode of inhibition depends upon the absence or presence of a templating nucleobase. Molecular modeling studies suggest that these analogues bind to the active site of reverse transcriptase as well as to a nearby hydrophobic binding pocket. Collectively, the studies using these non‐natural nucleotides reveal important mechanistic differences between representative high‐ and low‐fidelity DNA polymerases during nucleotide selection and incorporation.
Translational systems biology of inflammation and healing

Personalized medicine is a major goal for the future of healthcare, and we suggest that computational simulations are necessary in order to achieve it. Inflammatory diseases, both acute and chronic, represent an area in which personalized medicine is especially needed, given the high level of individual variability that characterizes these diseases. We have created such simulations, and have used them to gain basic insights into the inflammatory response under baseline, gene‐knockout, and drug‐treated experimental animals; for in silico experiments and clinical trials in sepsis, trauma, and wound healing; and to create patient‐specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation. Since they include both circulating and tissue‐level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ damage via tissue damage/dysfunction. We suggest that computational simulations are the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
Factors potentially affecting the function of kidney grafts

Background Donor and recipient risk factors on graft function have been well characterized. The contribution of demographic factors, such as age, gender, and other potential factors of donor and recipient at the time of transplantation on the function of a graft is much less well understood. In this study, we analyzed the effects of factors such as age, gender, etc., on the short‐term and long‐term graft function in kidney transplant recipients from living donor. Methods A total of 335 living donors and their recipients, who had kidney transplantation in our center from May 2004 to December 2009, were included. Serum creatinine level was used as the assessment criterion (serum creatinine level lower than 115 mmol/L is normal). Factors related to graft function such as age, gender, blood relation by consanguinity, human leukocyte antigen (HLA) mismatch, ABO type, etc., were analyzed separately. Results Donor age is the key factor affecting both the short‐term and long‐term function of a grafted kidney from a living donor. The group with donors younger than 48 years showed the best kidney function post transplantation. Match of gender and age is another important factor that influences the function of grafted kidney from a living donor. The older donor to younger recipient group had the worst outcome after kidney transplantation. After 36 months post transplantation, female donor to male recipient group had worse kidney function compared to other groups. We also found that calcinerin inhibitor used in the maintenance period may influence the function of a grafted kidney. No significant statistical differences were found in consanguinity, blood type, and mismatch of HLA. Conclusions Donor age is an important factor affecting the function of a grafted kidney from a living donor. We also recommend taking nephron, immunology factor, infection, and demographic information all into consideration when assessing the outcome of kidney transplantation.
Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice

Permanent scars form upon healing of tissue injuries such as those caused by ischemia (myocardial infarction, stroke), trauma, surgery, and inflammation. Current options in reducing scar formation are limited to local intervention. We have designed a systemically administered, target-seeking biotherapeutic for scar prevention. It consists of a vascular targeting peptide that specifically recognizes angiogenic blood vessels and extravasates into sites of injury, fused with a therapeutic molecule, decorin. Decorin prevents tissue fibrosis and promotes tissue regeneration by inhibiting TGF-β activity and by other regulatory activities. The decorin-targeting peptide fusion protein had substantially increased neutralizing activity against TGF-β1 in vitro compared with untargeted decorin. In vivo, the fusion protein selectively accumulated in wounds, and promoted wound healing and suppressed scar formation at doses where nontargeted decorin was inactive. These results show that selective targeting yields a tissue-healing and scar-reducing compound with enhanced specificity and potency. This approach may help make reducing scar formation by systemic drug delivery a feasible option for surgery and for the treatment of pathological processes in which scar formation is a problem.
Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: Recurrence or second primary tumor?

OBJECT In nearly all patients with glioblastoma multiforme (GBM) a local recurrence develops within a short period of time. In this paper the authors describe two patients in whom a second GBM developed after a relatively long time interval at a site remote from the primary tumor. The genetic profiles of the tumors were compared to discriminate between distant recurrence and a second primary tumor. METHODS Both patients harboring a supratentorial GBM were treated with surgery and local high-dose radiotherapy. Local control of the disease at the primary tumor site was achieved. Within 2 years, a second GBM developed in both patients, not only outside the previously irradiated target areas but infratentorially in one patient and in the opposite hemisphere in the other. The tumors were examined for the presence of several genetic alterations that are frequently found in GBMs--a loss of heterozygosity at chromosome regions 1p36, 10pl5, 19q13, and 22q13, and at the CDKN2A, PTEN, DMBT1, and TP53 gene regions; a TP53 mutation; and EGFR amplification. In the first patient, genetic profiling revealed that the primary tumor had an allelic imbalance for markers in several chromosome regions for which the second tumor displayed a complete loss. In the second patient, genetic profiling demonstrated the presence of genetic changes in the second tumor that were identical with and additional to those found in the primary tumor. CONCLUSIONS Based on the similarities between the genetic profiles of the primary and the second tumors in these patients, the authors decided that in each case the second distant GBM was a distant recurrence rather than a second independent primary tumor.
Surgical Treatment of Moderate Hallux Valgus: A Comparison of Distal Chevron Metatarsal Osteotomy With and Without Lateral Soft-Tissue Release

Purpose: The purpose of the study was to determine whether lateral soft-tissue release (LSTR) has a beneficial or detrimental effect on the outcome of distal Chevron first metatarsal osteotomy (DCMO) in the treatment of moderate hallux valgus (HV). Methods: We compared the effect of different surgical treatments in 2 groups of patients: group I (23 patients, 25 feet, average age of 55 [from 43 to 77] years) was subjected to DCMO only, whereas group II (18 patients, 23 feet, average age of 59 [from 52 to 70] years]) was subjected to DCMO with LSTR. The American Orthopaedic Foot and Ankle Society’s Hallux Metatarsophalangeal-Interphalangeal scale survey was conducted postoperatively, followed by the brief survey on postoperative patient satisfaction. The patient follow-up period was from 18 to 24 months after surgical treatment, on average. Results: After surgical intervention, both groups of patients presented with an improved HV angle, but there was no significant difference between the groups. However, group II showed significant improvements in medial sesamoid bone position and patient satisfaction scores as compared with group I. Conclusion: Our midterm follow-up of surgical treatments for moderate HV deformity suggests that both procedures provide good postoperative results. However, according to our results, DCMO with LSTR provides better results than procedures without LSTR. Levels of Evidence: Therapeutic, Level III: Retrospective comparative study