Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase 2 study of rituximab, cyclophosphamide, bortezomib and dexamethasone (R-CyBorD) in relapsed low grade and mantle cell lymphoma

Abstract In this phase 2 trial, we sought to evaluate the efficacy and safety of rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients with low-grade NHL. The regimen included rituximab on day 1 with weekly cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle. Twenty one patients were enrolled on the study. Median age was 69 years (range 51–80) and 17 (81%) patients had two or more prior treatments. Histologies included FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral sensory neuropathy were the most common adverse events. With a median follow-up of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months, respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients with an acceptable safety profile.
Work-to-non-work spillover: the impact of public service motivation and meaningfulness on outcomes in work and personal life domains

ABSTRACT This study examines why, and when, public service motivation (PSM) has spillover effects from employees’ work lives into their personal lives. Drawing on a dual conceptualization of meaningfulness, we propose and examine the relationship of PSM with meaningfulness of work through processes of realization and justification. Analyses of 253 matched dyads of policing employees and spouses support the proposed mediation effect of meaningfulness of work from PSM to job satisfaction, individual initiative (i.e. task-related behaviours after work), and psychological detachment from work in non-work time. Job autonomy is found to compensate for PSM in predicting meaningfulness and these outcomes.
Biosensors for Whole-Cell Bacterial Detection

SUMMARY Bacterial pathogens are important targets for detection and identification in medicine, food safety, public health, and security. Bacterial infection is a common cause of morbidity and mortality worldwide. In spite of the availability of antibiotics, these infections are often misdiagnosed or there is an unacceptable delay in diagnosis. Current methods of bacterial detection rely upon laboratory-based techniques such as cell culture, microscopic analysis, and biochemical assays. These procedures are time-consuming and costly and require specialist equipment and trained users. Portable stand-alone biosensors can facilitate rapid detection and diagnosis at the point of care. Biosensors will be particularly useful where a clear diagnosis informs treatment, in critical illness (e.g., meningitis) or to prevent further disease spread (e.g., in case of food-borne pathogens or sexually transmitted diseases). Detection of bacteria is also becoming increasingly important in antibioterrorism measures (e.g., anthrax detection). In this review, we discuss recent progress in the use of biosensors for the detection of whole bacterial cells for sensitive and earlier identification of bacteria without the need for sample processing. There is a particular focus on electrochemical biosensors, especially impedance-based systems, as these present key advantages in terms of ease of miniaturization, lack of reagents, sensitivity, and low cost.
Top 10 Research Questions Related to Children Physical Activity Motivation

Physical activity is critical to healthy development of children. It is well documented that helping children develop and sustain a physically active lifestyle requires children to become motivated. Many studies have been conducted in the past 2.5 decades on determinants and correlates for children and adolescents' physical activity motivation. The findings have informed researchers and practitioners about motivation sources for children and effective strategies to motivate children in given physical activity settings. Built on the extensive knowledge base and theoretical platforms formed by these research studies, the purpose of this article is to take a look at the current research landscape and provide subjective thoughts about what we still need to know about children's physical activity motivation. The product of this subjective thinking process rendered 10 potential questions for future research on children's physical activity motivation in both in-school and out-of-school settings. These topics encompass those focusing on children's physical activity motivation as a mental dispositional process, those conceptualizing the motivation as an outcome of person–environment interactions, and those attempting to dissect the motivation as an outcome of social–cultural influences and educational policies. It is hoped that the topics can serve researchers interested in children's physical activity motivation as starting blocks from which they can extend their conceptual thinking and identify research questions that are personally meaningful. It is also hoped that the list of potential questions can be helpful to researchers in accomplishing the imperative and significant mission to motivate children to be physically active in the 21st century and beyond.
The Role of Angiogenic and Wound Repair Factors During CMV‐Accelerated Transplant Vascular Sclerosis in Rat Cardiac Transplants

Human cytomegalovirus (HCMV) accelerates transplant vascular sclerosis (TVS), a consequence of angiogenesis (AG) and wound repair (WR). While HCMV can be localized to TVS lesions, the low number of infected cells suggests a global effect on target tissues. We used microarray analysis followed by real‐time‐polymerase chain reaction (RT‐PCR) in an RCMV‐accelerated TVS rat cardiac transplant model to determine whether CMV activates host WR and AG factors. Dysregulated cellular genes in allografts from RCMV‐infected recipients were compared to those from uninfected recipients and native hearts. We demonstrated that RCMV upregulates the genes involved in WR and AG, which was highest during the critical time of TVS acceleration (21–28 days). Using a standard in vitro AG assay, virus and serum‐free supernatants collected at 48 h postinfection significantly induced endothelial cell (EC) migration, branching and tubule formation compared to supernatants from mock‐infected cells. Supernatants from ultraviolet (UV)‐inactivated RCMV‐infected cells failed to induce AG, indicating that virus replication is required. Upregulation of WR and AG genes occurs during the critical period of CMV‐accelerated TVS. Targeting these genes may prevent this process and improve allograft survival.
The possible contribution of HIV-1-induced syncytia to the generation of intersubtype recombinants in vitro

Objective:To develop a method for single syncytia isolation and delineate the possible contribution of syncytia to intersubtype recombination. Design:We dually infected whole peripheral mononuclear blood cells with subtype A and D viruses and studied syncytia in vitro and developed a method to isolate individual syncytia to further study HIV variants/dual infections, viral isolation, proviral copies in single syncytia and possible intersubtype recombination in dual cultures containing syncytia using real time PCR. Methods:Cell culture-based single syncytia isolation, PCR and cloning to determine the nature of HIV variants and real-time PCR to determine proviral copies per individual syncytium and intersubtype recombination in dual cultures. Viral coculture from single syncytia and p24 antigen determination for assessing viral replication in vitro. Results:Our results show the feasibility that not only can single syncytia be successfully isolated, but the viruses from individual syncytia can also be grown in vitro. They also demonstrate the ability of single syncytia to bring diverse HIV-1 subtypes together along with the possible contribution to intersubtype recombination in vitro. Up to 40% of single syncytia harbored both input HIV-1 subtypes and single syncytium could harbor as many as 2000 proviral DNA copies, which exceeds the limit seen in a single cell. Conclusion:These analyses are unique in experimentally confirming the previously held belief that single syncytia can harbor multiple HIV strains and that they can serve as a breeding ground for heterozygous virions and this may contribute toward viral diversity and intersubtype recombination.
Fluid dynamics of nodal flow and left–right patterning in development

The manner in which the nodal flow determines the breaking of left–right symmetry during development is a beautiful example of the application of fluid dynamics to developmental biology. Detailed understanding of this crucial developmental process has greatly advanced by the transfer of ideas between these two disciplines. In this article, we review our and others' work on applying fluid dynamics and dynamical systems to the problem of left–right symmetry breaking in vertebrates. Developmental Dynamics 237:3477–3490, 2008. © 2008 Wiley‐Liss, Inc.
Tarificación óptima para el servicio de agua en las ciudades. Aplicación a tres municipios españoles

El principal objetivo de la Tesis Doctroal radica en el diseno de tarifas para el servicio municipal de suministro de agua en un contexto urbano. La fijacion de precios en este ambito ha de responder a una serie de objetivos previamente establecidos (OCDE, 1987, 1999). Las tarifas a contrastar estan basadas en los esquemas teoricos propuestos por Ramsey (1927) y Feldstein (1972). El trabajo ha planteado, como un primer paso necesario para el establecimiento de tarifas, la estuacion de la demanda de agua a nivel residencial y comercial/industrial, asi como los costes derivados de la actividad de suministro para las municipios de Sevilla, Elche (Alicante) y Gijon (Asturias). Actualmente, la investigacion se cierra con dos ejercicios de analisis de bienestar, comenzando por calcular las perdidas de bienestar, comenzando por calcular las perdidas de bienestar asociadas a medidas de racionamiento ejecutadas en Sevilla durante uno de los episodios de sequia mas recientes, terminando por abordar la comparacion de las tarifas propuestas con las vigenes en el ano 2000 para cada municipio en terminos de bienestar.
Mature results of an individualized radiation dose prescription study based on normal tissue constraints in stages I to III non-small-cell lung cancer.

PURPOSE We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach. PATIENTS AND METHODS In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0. RESULTS The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable. CONCLUSION Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.
Fine structure of mammalian renal cilia

Studies were carried out, using transmission electron microscopy, of the cilia of the nephrons of rat and human kidneys. Cilia were observed in the parietal layer of Bowman's capsule, in the proximal tubule, the distal tubule, including the macula densa, and the collecting duct. They had a number of characteristic features, including the presence of a centriole adjacent to the basal body, long, slender cross‐striated rootlets, and a typically organized basal body. The shaft of the cilia differed from the typical 9 + 2 pattern of organization. Near the base of the cilia the pattern was 9 + 0. In the middle portion, one or more of the peripheral doublets had been displaced centrally to give an 8 + 1 or a 7 + 2 pattern, while towards the tip the pattern became more irregular and the doublets were reduced to single microtubules. We have hypothesized that these cilia may be vestigial. They may, if motile, have some minor stirring function, or they may play a sensory role, as has been postulated for similarly structured cilia in other sites.
Visual analysis of frequent patterns in large time series

The detection of previously unknown, frequently occurring patterns in time series, often called motifs, has been recognized as an important task. To find these motifs, we use an advanced temporal data mining algorithm. Since our algorithm usually finds hundreds of motifs, we need to analyze and access the discovered motifs. For this purpose, we introduce three novel visual analytics methods: (1) motif layout, using colored rectangles for visualizing the occurrences and hierarchical relationships of motifs in a multivariate time series, (2) motif distortion, for enlarging or shrinking motifs as appropriate for easy analysis and (3) motif merging, to combine a number of identical adjacent motif instances without cluttering the display. We have applied and evaluated our methods using two real-world data sets: data center cooling and oil well production.
Haemodynamic evaluation of aortic regurgitation after transcatheter aortic valve implantation using cardiovascular magnetic resonance.

AIMS Echocardiography may underestimate the degree of paravalvular aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve bioprosthesis due to inherent limitations of ultrasound imaging in the evaluation of implanted cardiac prostheses. We aimed to evaluate the accuracy and feasibility of cardiovascular magnetic resonance (CMR) in quantifying regurgitant volume (RV) and regurgitant fraction (RF) in patients treated with this bioprosthesis for severe calcific aortic stenosis, and to compare the results with echocardiography and aortography. METHODS AND RESULTS This study included 16 patients with a mean age of 78.7 years (eight women, eight men) who underwent successful TAVI using Medtronic CoreValve bioprosthesis. AR was evaluated by CMR, echocardiography, and aortography. Angiography was performed immediately after valve implantation. CMR and echocardiography were performed four weeks after valve implantation. There was a highly significant correlation between the CMR-derived and the angiographically-estimated degree of AR (r=0.86, p<0.001). On the other hand, there was only a limited correlation between CMR and echocardiography (r=0.374, p=0.15) as well as angiography and echocardiography (r=0.319, p=0.23) regarding the degree of AR. The weighted kappa for agreement between echocardiography and angiography was 0.14, for agreement between echocardiography and CMR 0.20, and for agreement between angiography and CMR 0.72. Echocardiography underestimated AR by one degree compared to CMR in five patients and 2 degrees in two patients; in six of these, the degree of AR obtained by CMR was similar to angiography. CONCLUSIONS In patients undergoing TAVI, comparisons between purely quantitative measurements of AR by CMR and qualitative assessment by angiography showed better correlations than those with echocardiography. This suggests that echocardiography may underestimate the degree of AR and CMR in these circumstances has a great potential in reliably measuring the severity of AR in a quantitative manner.
Ghrelin suppression is associated with weight loss and insulin action following gastric bypass surgery at 12 months in obese adults with type 2 diabetes

Roux‐en‐Y gastric bypass (RYGB) surgery reverses type 2 diabetes mellitus (T2DM) in approximately 80% of patients. Ghrelin regulates glucose homeostasis, but its role in T2DM remission after RYGB surgery is unclear. Nine obese T2DM subjects underwent a mixed meal tolerance test before and at 1 and 12 months after RYGB surgery. Changes in ghrelin, body weight, glucagon‐like polypeptide‐1 (GLP‐1, glucose tolerance and insulin sensitivity (IS) were measured. At 1 month, body weight, glycaemia and IS were improved, while ghrelin concentrations were reduced (p < 0.05). After 12 months, body weight and fasting glucose were reduced (30 and 16%, respectively; p < 0.05) and IS was enhanced (threefold; p < 0.05). Ghrelin suppression improved by 32% at 12 months (p < 0.05), and this was associated with weight loss (r = 0.72, p = 0.03), enhanced IS (r = −0.78, p = 0.01) and peak postprandial GLP‐1 (r = −0.73, p = 0.03). These data suggest that postprandial ghrelin suppression may be part of the mechanism that contributes to diabetes remission after RYGB surgery.
Silencing NaTPI Expression Increases Nectar Germin, Nectarins, and Hydrogen Peroxide Levels and Inhibits Nectar Removal from Plants in Nature1[W][OA]

Native flower visitors removed less nectar from trypsin proteinase inhibitor (TPI)-silenced Nicotiana attenuata plants (ir-pi) than from wild-type plants in four field seasons of releases, even when the nectar repellant, nicotine, was also silenced. Analysis of floral chemistry revealed no differences in the emission of the floral attractants benzylacetone and benzaldehyde or in the concentrations of nectar sugar and nicotine between wild-type and ir-pi flowers, suggesting that these two lines are equally able to attract insect visitors. TPI activity was found in all wild-type flower parts and was highest in anther heads, while TPI activity was not found in any parts of ir-pi flowers. The nectar of ir-pi flowers contained 3.6-fold more total proteins than the nectar of wild-type flowers. Proteomics analysis and hydrogen peroxide (H2O2) measurements revealed that ir-pi nectar contained more nectarins and nectar germin-like proteins and about 1.5-fold more H2O2 compared with wild-type nectar. Field experiments with wild-type flowers supplemented with a solution containing sugar and glucose oxidase demonstrated a causal association between the accumulation of H2O2 and the reduction in nectar removal. These results showed that silencing TPI expression increases the accumulation of nectar proteins and H2O2 levels, which in turn reduces nectar removal by native insect floral visitors. The effect of silencing TPIs on nectar protein accumulation suggests an endogenous regulatory function for TPIs in N. attenuata flowers. The repellency of H2O2 to floral visitors raises new questions about the qualities of nectar that make it attractive for pollinators.
Are algal communities driven toward maximum biomass?

In this continental-scale study, we show that in major benthic and planktonic stream habitats, algal biovolume—a proxy measure of biomass—is a unimodal function of species richness (SR). The biovolume peak is observed at intermediate to high SR in the benthos but at low richness in the phytoplankton. The unimodal nature of the biomass–diversity relationship implies that a decline in algal biomass with potential harmful effects on all higher trophic levels, from invertebrates to fish, can result from either excessive species gain or species loss, both being common consequences of human-induced habitat alterations. SR frequency distributions indicate that the most frequent richness is habitat-specific and significantly higher in the benthos than in the plankton. In all studied stream environments, the most frequent SR is lower than the SR that yields the highest biovolume, probably as a result of anthropogenic influences, but always within one standard deviation from it, i.e. they are statistically indistinguishable. This suggests that algal communities may be driven toward maximum biomass.
Negative regulation of mitogen‐stimulated, anchorage‐independent cell growth by a tumor‐suppressor gene function

Immortal, nontumorigenic cell lines of Syrian hamster embryo (SHE) cells with different tumor‐suppressing activity were isolated. Subclones from the parental cells were isolated that either had retained (supB+) or lost (supB−) the ability to suppress tumorigenicity after hybridization with tumor cells. The growth properties of these cells were studied to determine how this tumor‐suppressor gene function influences cell growth. When the cells were grown on plastic, their growth properties were similar, and neither cell type grew in soft agar containing 10% serum, which supported the growth of tumorigenic cells. However, in agar supplemented with growth factors and 10% serum, supB− cells formed colonies whereas supB+ cells did not. Efficient growth (colony‐forming efficiencies greater than 20%) of supB− cells was obtained in agar supplemented with serum and a combination of epidermal growth factor (EGF), platelet‐derived growth factor (PDGF), and insulin (EPI) or with serum and basic fibroblast growth factor (BFGF). The effect of EPI and bFGF together was additive. supB+ cells failed to grow under any of these conditions, suggesting that the suppressor gene function blocked the growth response of the cells to multiple growth factors when the cells were suspended in agar. In SupB− cells, transforming growth factor‐β1 and retinoic acid inhibited anchorage‐independent growth response to EPI but not the growth response to bFGF. These observations are consistent with the hypothesis that bFGF stimulates the growth of supB− cells by a signal transduction pathway that differs from the pathway stimulated by EGF or PDGF. Thus, this suppressor gene function may regulate anchorage‐independent growth at some common point in signal transduction for multiple mitogens.
Questionnaire for the identification of back pain for epidemiological purposes.

OBJECTIVES--To design a questionnaire for the identification and assessment of severity of back pain for epidemiological purposes, and gain preliminary experience of its use. METHODS--A group of specialists, experienced in the epidemiology and clinical assessment of back pain, designed the questionnaire, and tested it individually. It was also given cross sectionally by interview to a population of male coal mine workers. RESULTS--The questionnaire comprised a maximum of 12 questions on the presence, radiation, frequency, and severity of back pain with reference to difficulty with specific activities, interference with normal work, and absence from work. 471 coal miners answered the questionnaire (66% of those invited). 56% (265 men) of the responders reported pain or ache in the back during the previous 12 months, and the incidence of first ever attacks during the same period was reported to be 34%. 69% reported having had back pain at some time. The responses to the questionnaire were partially validated by comparison with certified sickness absence for two days or more attributed to back pain. In men who were symptomatic in the previous 12 months, for the question relating to absence from work because of back pain, the sensitivity was 82% and specificity was 84%. CONCLUSION--The questionnaire is easy to administer and generates clear cut data that could be useful for epidemiological or screening purposes. Preliminary, limited, studies of its validity are reasonably encouraging, although further validation is required. It is hoped that researchers will find the questionnaire useful, will extend its validation, and continue to develop it.