Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Azithromycin in Combination with Other Antimalarial Drugs against Plasmodium falciparum In Vitro

ABSTRACT Initial field malaria prophylaxis trials with azithromycin revealed insufficient efficacy against falciparum malaria to develop azithromycin as a single agent. The objective of this in vitro study was to determine the best drug combination(s) to evaluate for future malaria treatment and prophylaxis field trials. In vitro, azithromycin was tested in combination with chloroquine against 10 representative Plasmodium falciparum isolates. Azithromycin was also assessed in combination with eight additional antimalarial agents against two or three multidrug-resistant P. falciparum isolates. Parasite susceptibility testing was carried out with a modification of the semiautomated microdilution technique. The incubation period was extended from the usual 48 h to 68 h. Fifty percent inhibitory concentrations (IC50s) were calculated for each drug alone and for drugs in fixed combinations of their respective IC50s (1:1, 3:1, 1:3, 4:1, 1:4, and 5:1). These data were used to calculate fractional inhibitory concentrations and isobolograms. Chloroquine-azithromycin studies revealed a range of activity from additive to synergistic interactions for the eight chloroquine-resistant isolates tested, while an additive response was seen for the two chloroquine-sensitive isolates. Quinine, tafenoquine, and primaquine were additive to synergistic with azithromycin, while dihydroartemisinin was additive with a trend toward antagonism. The remaining interactions appeared to be additive. These results suggest that a chloroquine-azithromycin combination should be evaluated for malaria prophylaxis and that a quinine-azithromycin combination should be evaluated for malaria treatment in areas of drug resistance.
Inactivation of LLC1 gene in nonsmall cell lung cancer

Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5‐aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis. © 2007 Wiley‐Liss, Inc.
Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder.

PURPOSE We describe cyclooxygenase-2 (COX-2) expression patterns in patients with carcinoma in situ and/or stage T1 transitional cell carcinoma. We determined whether expression is associated with clinical outcome in these patients. MATERIALS AND METHODS Immunostaining for COX-2 was performed on paraffin embedded bladder biopsy specimens from 2 independent groups of patients without muscle invasive carcinoma, including 39 with carcinoma in situ and 34 with stage T1 tumors. Immunoreactivity was scored as the percent of carcinoma in situ cells with cytoplasmic staining for COX-2 in the carcinoma in situ group and as the percent of stage T1 cells expressing COX-2 in the stage T1 transitional cell carcinoma group. We evaluated other molecular alterations, including E-cadherin, p21 and p53, because evidence suggests a biological association of COX-2 with alterations in these molecular markers. RESULTS In the carcinoma in situ group 5 patients (13%) had no immunoreactivity, while 2 (5%), 5 (13%) and 27 (69%) had 10%, 20% and 30% or greater carcinoma in situ cells positive for COX-2, respectively. In the transitional cell carcinoma group 1 (3%), 4 (12%) and 29 (85%) patients had 10%, 20% and 30% or greater positive cells, respectively. COX-2 expression was not associated with any clinical or pathological parameters, or with molecular markers regardless of the cutoff used. It was also not associated with clinical outcomes in the stage T1 transitional cell carcinoma group. In the carcinoma in situ group COX-2 expression was significantly associated with disease recurrence using cutoffs of 0% and greater than 10% positive cells, and with disease progression using a greater than 20% cutoff. However, it was not associated with bladder cancer related survival. CONCLUSIONS COX-2 is expressed in a high percent of patients with carcinoma in situ and stage T1 transitional cell carcinoma, supporting the rationale for chemoprevention studies with selective COX-2. We could not substantiate a role for COX-2 immunohistochemistry for the staging and prognosis of carcinoma in situ and/or stage T1 transitional cell carcinoma.
Rapid weight gain in professional boxing and correlation with fight decisions: analysis from 71 title fights

ABSTRACT Objectives: Boxing is a sport where athletes compete in several weight categories. Professional boxers typically dehydrate to cut their weight for the weigh-in (24 h before the contest) and then rehydrate before the fight. The International Boxing Federation (IBF) mandates a second weigh-in 12 h before the fight. Our objectives were: 1) To quantify the weight gain (WG) from the 1st to the 2nd weigh-in; 2) to investigate whether rapid WG affects boxing performance (win/loss rate) and 3) whether weight discrepancy (WD) 15 between boxers exposes them to increased health risks (rate of fights ended before time limit). Methods: From official weigh-in reports of 71 IBF fights (142 fighters) the following data were gathered/calculated for each boxer: age, weight division, 1st weight, 2nd weight, WG between weigh-ins (kg and %), WD between opponents, and fight decision. Results: Between the weigh-ins, the average WG was 2.52 ± 1.37 kg (range −0.3/6.4 kg) and 3.8 ± 2.2% of the initial body weight (range −0.4/9.3%) and the average WD 1.94 ± 1.50 kg (maximum 7.10 kg). Both WG and WD did not affect match outcomes. We observed tendencies for higher loss rate among boxers gaining more weight, and for higher victory rate in boxers with larger WD, however without reaching significance. A significant negative correlation was found between the 1st weight and the WG, both in absolute (r = −0.278, p = 0.001) and relative value (r = −0.497, p < 0.0001). Conclusions: Although correlations between WG, WD and boxing performance were not found, single cases with an alarming high WG and WD were noted.
An overview of approaches to second language acquisition and instructional practices

The purpose of this report is to contribute to the development of an evidence base for the teaching of Welsh as a second language in primary and secondary schools in Wales by presenting a critical overview of methods and instructional practices of second language teaching and considering their relevance to the Welsh context. It aims to both help stakeholders develop a better understanding of the key issues in second language teaching and learning and to lay out the critical factors to be considered in the reform of the Welsh language curriculum.
Decreased protein tyrosine phosphorylation and membrane fluidity in spermatozoa from infertile men with varicocele

Varicocele is a prevalent pathology among infertile men. The mechanisms linking this condition to infertility, however, are poorly understood. Our previous work showed a relationship between sperm functional quality and the ability of spermatozoa to respond to capacitating conditions with increased membrane fluidity and protein tyrosine phosphorylation. Given the reported association between varicocele, oxidative stress, and sperm dysfunction, we hypothesized that spermatozoa from infertile patients with varicocele might have a combined defect at the level of membrane fluidity and protein tyrosine phosphorylation. Semen samples from infertile patients with and without grade II/III left varicocele were evaluated for motion parameters (computer‐assisted semen analysis [CASA]), hyperactivation (CASA), incidence and intensity of protein tyrosine phosphorylation (phosphotyrosine immunofluorescence and western blotting), and membrane fluidity (Laurdan fluorometry), before and after a capacitating incubation (6 hr at 37°C in Ham's F10/BSA, 5% CO2). Spermatozoa from varicocele samples presented a decreased response to the capacitating challenge, showing significantly lower motility, hyperactivation, incidence and intensity of tyrosine phosphorylation, and membrane fluidity. The findings reported in this article indicate that the sperm dysfunction associated to infertile varicocele coexists with decreased sperm plasma membrane fluidity and tyrosine phosphorylation. These deficiencies represent potential new pathophysiological mechanisms underlying varicocele‐related infertility. Mol. Reprod. Dev. 73: 1591–1599, 2006. © 2006 Wiley‐Liss, Inc.
Histometrics: Improvement of the dynamic range of fluorescently stained proteins resolved in electrophoretic gels using hyperspectral imaging

Most image‐based analyses, using absorbance or fluorescence of the spatial distribution of identifiable structures in complex biological systems, use only a very small number of dimensions of possible spectral data for the generation and interpretation of the image. We here extend the concepts of hyperspectral imaging, being developed in remote sensing, into analytical biotechnology. The massive volume of information contained in hyperspectral spectroscopic images requires multivariate analysis in order to extract the chemical and spatial information contained within the data. We here describe the use of multivariate statistical methods to map and quantify common protein staining fluorophores (SYPRO Red, Orange and Tangerine) in electrophoretic gels. Specifically, we find (a) that the `background’ underpinning limits of detection is due more to proteins that have not migrated properly than to impurities or to ineffective destaining, (b) the detailed mechanisms of staining of SYPRO red and orange are apparently not identical, and in particular (c) that these methods can provide two orders of magnitude improvement in the detection limit per pixel, to levels well below the limit observable optically.
Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy, characterized by an almost complete loss of adipose tissue and severe insulin resistance. BSCL2 is caused by loss-of-function mutations in the BSCL2/SEIPIN gene, which is upregulated during adipogenesis and abundantly expressed in the adipose tissue. The physiological function of SEIPIN in mature adipocytes, however, remains to be elucidated. Here, we generated adipose-specific Seipin knockout (ASKO) mice, which exhibit adipocyte hypertrophy with enlarged lipid droplets, reduced lipolysis, adipose tissue inflammation, progressive loss of white and brown adipose tissue, insulin resistance, and hepatic steatosis. Lipidomic and microarray analyses revealed accumulation/imbalance of lipid species, including ceramides, in ASKO adipose tissue as well as increased endoplasmic reticulum stress. Interestingly, the ASKO mice almost completely phenocopy the fat-specific peroxisome proliferator–activated receptor-γ (Pparγ) knockout (FKO-γ) mice. Rosiglitazone treatment significantly improved a number of metabolic parameters of the ASKO mice, including insulin sensitivity. Our results therefore demonstrate a critical role of SEIPIN in maintaining lipid homeostasis and function of adipocytes and reveal an intimate relationship between SEIPIN and PPAR-γ.
The Impact of Corporate Reputation in a Dairy Company

The purpose of this paper is to understand the importance of corporate reputation (CR) how main intangible asset of a company. This study investigates the role of CR on optical three group’s stakeholders: cooperants, workers and customers on loyalty in cooperative organizations. This study proposes a theoretical model tested using structural equation modeling. 1200 valid questionnaires were collected from a three group samples: cooperants; workers and customers of the biggest dairy union of cooperatives in Iberia. CR has a significant impact on loyalty in three group’s stakeholders on organizations cooperatives. Corporate reputation is revealed as an intangible asset, constituting, as the pillar of organizational development by providing ability to compete in the market and generate profits. This study is based on three cross-sectional data from a dairy company. This is a topic that, given the multiplicity of possible approaches, it is even less studied the theoretical level as regards the analysis of corporate reputation with applicability in the various organizational stakeholders. The results give new guidelines to redress the cooperatives traditional management, namely the management of intangible assets like reputation. This paper contributes to the competitiveness of a type of organization closed to the social structure of the rural population. This research with three types of stakeholders (cooperants, customers and workers) power shall be constituted as an important contribution to the literature, for what has been analyzed only works strand of customers (external) and/or employees (internal). The results bring the management challenges of the 21st century to the traditional principles underlying cooperatives management helping them to reinforce competitiveness. The intangibility is always a difficult area of research, in which old doors close and new doors open.
Towards an Evolutionary Understanding of the Current Global Socio-Economic Crisis and Restructuring: From a Conjunctural to a Structural and Evolutionary Perspective

The current global socio-economic crisis and restructuring reshapes the terms of study of the global dynamics as a whole. A new generation of interdisciplinary socio-economic research on the matter in question seems to be progressively emerging in international literature. Against this background, it gradually emerges the understanding, that any attempt to interpret the individual contemporary socio-economic phenomena, which relate to the crisis and the attempt to restructure globalization, can only be inadequate and ineffective, since it fails to fully approach the current dynamics of globalization in synthetic, holistic terms. In this direction, new interpretative approaches seem to intensify interpenetration and conceptual syntheses between the different fields of socio-economic sciences, in an increasingly unified perspective, by extensively "borrowing" –in a direct and indirect way– methods and theoretical "lenses" derived from system science, chaos theory, and evolutionary economics. In the depth of this methodological rearrangement, according to the position put forward in the following paper, it is crucial that an effort is made to move from a conjunctural to a structural perception of the crisis. Ultimately, the great challenge for the field of study of global dynamics nowadays is the transition from the methodological principles of the traditional mechanistic interpretative method to a coherent and integrated evolutionary socio-economic perspective.
Is the WTO Dispute Settlement Procedure Fair to Developing Countries?

Since the inception of the World Trade Organization (WTO) in 1995, member countries have been heavily relying on the organization's dispute settlement procedure (DSP). Exploiting a new database on WTO litigations between 1995 and 2014, this paper describes disputes initiated over this period and identifies potential sources of bias concerning the participation of developing countries. The analysis builds on three different models to determine country i's probability of initiating a dispute against country j. Either it depends only on the two countries' structure of trade, that is the number of products exported by i to j (a situation we refer to as the rules-based model), or it is also affected by country i's or country j's specific characteristics (the unilateral power-based model), or it is also affected by bilateral economic and trade relations between countries i and j (the bilateral power-based model). We find that country i's structure of trade with j plays an important role in explaining the probability that i initiates a dispute against j under the DSP. Furthermore, country i's legal capacity and both countries' political regimes also affect this probability. However, we do not find that bilateral relationships between i and j, such as participants' capacity to retaliate against each others have an impact on dispute initiation.
Using Ethnography to Understand How Policy Reform Influences the Transfer Process at One Community College

Author(s): Felix, Eric R. | Abstract: A critical function of community college is providing students with pathways to a bachelor’s degree through transfer. Although students hold high aspirations of transferring, their rates of success are extremely low. In California, policymakers have used legislation as a primary mechanism of addressing transfer inefficiencies in the state’s tiered higher education system. This article explores the ways that recent state-level reform policy SB-1440 (Student Transfer Achievement Reform Act, 2010)—intended to streamline the transfer process through Associate Degrees for Transfer—affected existing practices, practitioners, and transfer-seeking students at one community college. Employing an ethnographic approach, this study highlights the interaction between the existing context and policy mandates that reshape campus transfer culture. The findings indicate that, although the transfer policy reform was intended to improve transfer pathways for students, there was a disconnect between students’ aspirations and the state higher education institutions accepting these Associate Degrees for Transfer. Additionally, there was a misalignment between campus practitioners’ efforts to implement transfer reform and students’ awareness of improvements. To compensate for this disconnect, students formed a student counter-space. These findings suggest the need for transformative higher education policy, built upon concepts of transfer infrastructure, to improve college opportunities and outcomes for students across the state.
Thyroarytenoid Muscle: Functional Subunits Based on Morphology and Muscle Fiber Typing in Cats

Using parvalbumin immunohistochemistry to determine the distribution of muscle fiber types in the feline thyroarytenoid muscle (TA), we clearly distinguished the vocalis (with predominance of “slow” type 1 fibers) from the external TA (in which “fast” type 2 fibers predominated, especially in its rostral part). Reconstruction of serial frontal sections of the TA allowed the stereoscopic study of each division. The existence of a rudimentary laryngeal ventricle separating the true and false vocal folds in cats was demonstrated anatomically and histologically, and its relationships to each division of the TA were established. Our results suggest that the vocalis, fitted for enduring activities, is suited for voice control. The fast, rostral part of the external TA seems suited to laryngeal sphincteric demands, while its caudal counterpart may act in both functions. The anatomic individualization of the divisions of the TA may suggest that they play distinct physiological roles and may imply that they should not be considered a single functional unit.
Lateral Column Lengthening Using Allograft Interposition and Cervical Plate Fixation

Lateral column lengthening has been used successfully in the treatment of stage II adult-acquired pes planovalgus deformity. The purpose of this study is to review the union rate when allograft material is used and the osteotomy stabilized with a cervical plate. A retrospective review was performed on 28 feet in 26 patients who underwent correction of stage II pes planovalgus deformity using a lateral column lengthening with allograft tricortical iliac crest stabilized with a cervical plate. Patients were evaluated preoperatively and postoperatively using a modified American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and the Short Form–12 health survey, as well as radiographically by assessing the talonavicular coverage angle. At a mean follow-up of 9 months, the mean total modified AOFAS score and pain subscore were significantly higher (45.6 and 25.0, respectively) versus preoperatively (27.3 and 11.2, respectively). Graft incorporation occurred in all but one case, and the average length of time to union was 10.06 weeks. Complications included 4 hardware removals, 1 nonunion, 1 graft penetration of the calcaneocuboid joint, and 2 cases of calcaneocuboid joint arthritis. Lateral column lengthening using allograft tricortical iliac crest bone graft with cervical plate fixation is a viable option for the correction of acquired pes planovalgus deformity. Allograft bone avoids donor site morbidity of autogenous iliac crest grafts and was not shown to increase rates of nonunion. Cervical plate fixation avoids the necessity of penetrating the graft with a screw and is associated with high patient satisfaction and radiographic union
Arthroscopically Pertinent Landmarks for Tunnel Positioning in Single-Bundle and Double-Bundle Anterior Cruciate Ligament Reconstructions

Background: Quantification of the overall anterior cruciate ligament (ACL) and anteromedial (AM) and posterolateral (PL) bundle centers in respect to arthroscopically pertinent bony and soft tissue landmarks has not been thoroughly assessed. Hypothesis: A standardized anatomical measurement method can quantitate the locations of the ACL and AM and PL bundle centers in reference to each other and anatomical landmarks. Study Design: Descriptive laboratory study. Methods: Quantification of the ACL and its bundle attachments was performed on 11 cadaveric knees using a radio frequency-tracking device. Results: The tibial ACL attachment center was 7.5 mm medial to the anterior horn of the lateral meniscus, 13.0 mm anterior to the retro-eminence ridge, and 10.5 mm posterior to the ACL ridge. The femoral ACL attachment center was 1.7 mm proximal to the bifurcate ridge and 6.1 mm posterior to the lateral intercondylar ridge. The tibial AM attachment center was 8.3 mm medial to the anteromedial aspect of the lateral meniscus anterior horn, 17.8 mm anterior to the retro-eminence ridge, and 5.6 mm posterior to the ACL ridge. The femoral AM attachment center was 4.8 mm proximal to the bifurcate ridge and 7.1 mm posterior to the lateral intercondylar ridge. The tibial PL bundle attachment center was 6.6 mm medial to the posteromedial aspect of the lateral meniscus anterior horn, 10.8 mm anteromedial to the root attachment of the lateral meniscus posterior horn, and 8.4 mm anterior to the retro-eminence ridge. The femoral PL bundle attachment center was 5.2 mm distal to the bifurcate ridge and 3.6 mm posterior to the lateral intercondylar ridge. Conclusion: The authors developed a comprehensive compilation of measurements of arthroscopically pertinent bony and soft tissue landmarks that quantitate the ACL and its individual bundle attachment centers on the tibia and femur. Clinical Relevance: These clinically relevant arthroscopic landmarks may enhance single- and double-bundle ACL reconstructions through improved tunnel placement.