Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Trabectedin With Irinotecan, Leucovorin and 5-Fluorouracil Arrests Primary Colorectal Cancer in an Imageable Patient-derived Orthotopic Xenograft Mouse Model

Background/Aim: The aim of the present study was to determine the efficacy of trabectedin combined with FOLFIRI (irinotecan, leucovorin and 5-fluorouracil) on a colorectal cancer (CRC) patient-derived orthotopic xenograft (iPDOX) mouse model. Materials and Methods: A CRC tumor from a patient previously established in nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Mice were randomized into four groups: Group 1, untreated control; group 2, FOLFIRI; group 3, trabectedin alone; group 4, trabectedin plus FOLFIRI. Tumor width, length, and mouse body weight was measured twice every week. Results: All three treatment groups showed inhibited tumor growth compared to the untreated control group. Only the combination of FOLFIRI and trabectedin arrested tumor growth. No significant changes was observed in body weight in any group. Conclusion: These findings suggest that the combination of trabectedin plus FOLFIRI has clinical potential for patients with CRC.
The Long-Term Efficacy of Suicide Prevention Gatekeeper Training: A Systematic Review

The practice of educating individuals (known as ‘gatekeepers’ [GK]) at the informal social level with the knowledge, skills, and confidence to identify an at-risk individual and provide support has been shown as an effective suicide prevention method. Despite the efficacy of gatekeeper training (GKT) in the short-term, there are concerns over the long-term efficacy of these outcomes. The objective of this review was to identify the empirical GKT studies in the literature that included evaluations at pre, post, and follow-up. Additionally, this review aimed to evaluate the long-term effect of training on GK behavior. PubMed, Cochrane Library, and PsycNET databases were searched using the terms ‘gatekeeper’ and ‘suicid*’ present in the title and/or the abstract, with the terms ‘follow-up’, ‘pre-post’, or ‘long-term’ present in any text. Studies must have involved a suicide prevention program intervention provided to general members of the community. Knowledge and self-efficacy were shown to exhibit the strongest endurance of training effect, although some decay was present for knowledge over time (M follow-up delay 6.1 months). Gatekeeper attitude at follow-up (M follow-up delay 4.4 months) had returned to baseline levels in 57% (4/7) of the identified studies that evaluated this construct. Behavioral intention and behavior both indicate a weak training effect with poor translation of training into intervention behavior. Findings indicate the ideological and socio-cultural aspects of individual GKs should also be addressed to facilitate the improved potential for long-term attitudinal change. Future research directions are discussed.
Microsatellite Instability and Survival in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis

Background/Aim: About 15-20% of colorectal cancers (CRCs) have deficiency in a mismatch repair (MMR) protein. MMR has a high level of microsatellite instability (MSI-H). We have conducted this review and meta-analysis to determine the prognostic role of MSI-H status in stage II CRC. Materials and Methods: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, and SCOPUS for studies reporting data on overall survival (OS) and disease-free or relapse-free survival (DFS or RFS) for MSI-H compared to microsatellite stable (MSS) CRC. Results: A total of 39 studies were analysed, including 12,110 patients. MSI-H status was associated with a significantly reduced risk of death (HR=0.64, 95%CI=0.52-0.8, p<0.01) and relapse (HR=0.59, 95%CI=0.45-0.77, p<0.01) in stage II CRC. Conclusion: MSI-H represents an important prognostic determinant in stage II CRC and may be considered when estimating the risk of recurrence in stage II CRC.
Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance

ABSTRACT An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing antibody (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses.
Distinct rates and patterns of spread of the major HIV-1 subtypes in Central and East Africa

Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.
Vitamin B2 and Folate Concentrations are Associated with ARA, EPA and DHA Fatty Acids in Red Blood Cells of Brazilian Children and Adolescents

Vitamins B2, B6, B12, and folate are essential for methylation reactions and possibly influence the transport of polyunsaturated fatty acids in plasma and red blood cells (RBC). Associations between B-vitamin biomarkers and fatty acid (FA) profile were analyzed in Brazilian children and adolescents. This cross-sectional study included 249 children and adolescents, aged 9–13 years old. Dietary intake was assessed by the food frequency questionnaire and the healthy eating index (HEI). Biomarkers for vitamins B2, B6, B12, and folate were measured in plasma. The FA profile and the metabolites of one-carbon metabolism were measured in RBC. Associations were tested with multiple linear regression models. An increase of 1 nmol/L in vitamin B2 was associated with an increase of 0.19 mg/dL of EPA, 0.20 mg/dL of ARA, and 0.25 mg/dL of DHA in RBC. An increase of 1 ng/mL in plasma folate was associated with an increase of 0.14 mg/dL of EPA, 0.22 mg/dL of ARA, and 0.21 mg/dL of DHA in RBC. These findings highlight the importance of an adequate intake of vitamin B2 and folate in childhood, since they may improve the FA profile in RBCs and may help prevent cardiovascular disease.
Protection of Dairy Cattle in the EU: State of Play and Directions for Policymaking from a Legal and Animal Advocacy Perspective

Simple Summary This paper presents the regulatory instruments applicable to the protection of dairy cattle in the EU and summarizes the available evidence, pointing to some serious shortcomings in enforcing the law. Corrective measures are proposed from a legal and animal advocacy perspective, with additional considerations on best practice and directions for future developments in legislation and good practice. Abstract With the exception of a detailed Directive for calves, the welfare of dairy cattle is not regulated by species-specific legislation in the European Union. Their basic protection falls under the provisions of Directive 98/58/EC, also known as the “General Farm Animals Directive”. Article 3 of this Directive states: “Member States shall make provision to ensure that the owners or keepers take all reasonable steps to ensure the welfare of animals under their care and to ensure that those animals are not caused any unnecessary pain, suffering or injury”. However, recent reports show that the welfare of dairy cows in the EU is not sufficiently monitored and that serious problems persist. Lameness, mastitis, cubicle design, flooring, cleanliness, and permanent tethering remain critical areas. We argue that, to demonstrate compliance with Article 3 of Directive 98/58, farmers and Member States should urgently address these issues. The increasing proportion of cows that are never allowed to graze and high milk yields are also reasons for concern and will need to be addressed as a matter of priority in future EU guides to good practice and, eventually, legislation.
A Bioinspired Twin Inverted Multiscale Matched Filtering Method for Detecting an Underwater Moving Target in a Reverberant Environment

To this day, biological sonar systems still have great performance advantages over artificial sonar systems, especially for detection in environments with clutter, strong reverberation, and a low signal to noise ratio (SNR). Therefore, mammal sonar systems, for instance, bats and toothed whales, have many characteristics worth learning from. This paper proposes a bioinspired twin inverted multiscale matched filtering method to detect underwater moving targets. This method can be mainly divided into three parts. Firstly, a hyperbolic frequency modulation (HFM) continuous wave (CW) multiharmonic detection signal was adopted after analyzing signals from bats and dolphins. This signal combines the advantages of CW and HFM signals and has excellent time measurement and speed measurement performance when detecting a moving target. Secondly, the twin inverted waveform was introduced to suppress strong linear reverberation and highlight moving targets. The pulse interval was determined by assessing the reverberation reduction time. Thirdly, when processing echoes, a multiscale matched filtering method was proposed to make use of multiharmonic information and improve detection performance. Finally, a channel pool experiment was carried out to test the performance of the proposed method. The experimental result demonstrates that the proposed method has better performance when detecting a moving target in a reverberant environment compared to the conventional matched filtering method. Related results can be applied to small underwater platforms or sensor network platforms for target detection and coastal defense applications.
MCCIP ARC Science Review 2010-11 Plankton

The important decadal climate indicator for the North Atlantic, the North Atlantic Oscillation (NAO), has been generally rising (with occasional negative NAO years) along with Northern Hemisphere Temperatures over the past 30 years and the surface waters of the European Continental shelf have been warming. This has caused extensive changes in the planktonic ecosystem in terms of plankton production, biodiversity, and species distribution which have had effects on fisheries production and other marine life (e.g. seabirds) (Reid & Edwards, 2001; Edwards et al., 2001, 2002; Beaugrand et al., 2003, 2004; Richardson & Schoeman, 2004; Southward et al., 2004; Alheit et al., 2005; Heath, 2005) .
Randomized, Double-Blind, Pharmacokinetic Equivalence Trial Comparing DRL-Rituximab With MabThera in Patients With Diffuse Large B-Cell Lymphoma

PURPOSE We sought to compare the pharmacokinetics (PKs) of DRL-rituximab (DRL_RI; potential biosimilar) and innovator rituximab MabThera (Roche, Grenzach-Wyhlen, Germany; reference medicinal product [RMP]) in patients with diffuse large B-cell lymphoma (DLBCL). Efficacy, pharmacodynamics (PDs), safety, and immunogenicity were also compared. PATIENTS AND METHODS We conducted a double-blind, parallel-group study in patients with untreated DLBCL who were eligible to receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy. Patients were randomly assigned at a one-to-one ratio to receive DRL_RI or RMP for six 21-day cycles of rituximab plus CHOP, with 18 months of follow-up after day 1, cycle 6 (C6). Primary end point was C1 PKs, measured as area under the plasma concentration–time curve from day 0 to 21 (AUC0-21 days) and maximum plasma concentration (Cmax). Equivalence was defined as 90% CIs for the DRL_RI/RMP geometric mean ratios (GMRs) within 80% and 125%. Secondary end points included efficacy noninferiority measured by objective response rate (ORR) at C6 and event-free survival and overall survival at 87 weeks, PK equivalence at C6 and PD equivalence (rate of B-cell depletion and repletion), safety, and immunogenicity. The trial was stopped after sufficient patients for primary end point evaluation were enrolled. Secondary end points are reported as observed. RESULTS A total of 151 patients were randomly assigned (DRL_RI, n = 76; RMP, n = 75). DRL_RI/RMP GMRs for AUC0-21 days and Cmax in C1 were 99.77 (90% CI, 87.60 to 113.63) and 96.19 (90% CI, 88.65 to 104.38), respectively. ORR at C6 for DRL_RI and RMP were 82.0% and 84.8%, respectively. Rates of B-cell depletion/repletion, immunogenicity, and adverse events were comparable in both groups. CONCLUSION DRL_RI and RMP had equivalent PKs, with comparable efficacy, PDs, safety, and immunogenicity.
Design of a Tunable Absorber Based on Active Frequency-Selective Surface for UHF Applications

An ultrathin tunable absorber for the ultrahigh frequency (UHF) band is presented in this paper. The absorber is a single-layer structure based on the topology of a Salisbury screen, in which the conventional resistive layer is replaced by an active frequency-selective surface (AFSS) loaded with resistors and varactors. The reflectivity response of the absorber can be controlled by adjusting the reverse bias voltage for the varactors, which is verified by both simulated and measured results. The experimental results show that the reflectivity response of the absorber can be modulated below −10 dB over a frequency band ranging from 415 to 822 MHz. The total thickness of the absorber, 10 mm, is equivalent to only λ/72 of the lower limit frequency. The absorbing mechanism for the designed absorber is illustrated by simulating the volume loss density distributions. A detailed analysis is also carried out on the basis of these parameters, such as the AFSS shape, resistor, thickness of the foam, thickness and permittivity of the dielectric substrate, and incident angles, which contribute to the reflectivity of the AFSS absorber.
Soil Carbon Storage and Its Determinants in Forest Fragments of Differentiated Patch Size

Research Highlights: Soil carbon storage (SOC) decreased due to forest fragmentation through lower proportion of macroaggregate distribution, higher storage of fine roots and litter falls, and lower fine root production rate. Background and Objectives: Globally, forest fragmentation processes lead to enormous losses of SOC in forests. We investigated SOC and its determinants in forest fragments experiencing edge disturbances in south China. Materials and Methods: Soil aggregate characteristics, dynamics of fine roots, and litter fall were studied from forest edges to interiors. Generalized linear mixed models were used to model the contributions of fine root and litter fall dynamics to carbon concentration in aggregates. Results: Large and small macroaggregates had higher proportion of aggregate distribution and contributed more carbon to SOC in all types of plots in the present study. SOC significantly increased from forest edges to interiors due to carbon concentration of these two aggregate types increasing from edges to interiors, while the proportion of different aggregate distributions was similar within each plot. The same trend was found with increasing forest patch size. Fine root biomass storage had the strongest impact on carbon concentration in large macroaggregates and microaggregates, with higher fine root biomass storage associated with lower carbon concentration. In addition, biomass storage and production rates of both fine roots and litter falls decreased from forest interiors to edges. Our results showed that SOC was significantly decreased due to the lower proportion of large and small macroaggregate distribution, and lower fine root production rate in forest fragments. Conclusions: SOC loss due to effects of forest fragmentation and forest edges occurred through decreased concentrations of soil aggregates and fine root production rates. Results from this study will enhance our ability to evaluate soil aggregate, fine root, and leaf litter fall contributions to SOC within forest fragments, and to suggest basic recommendations for the management and conservation of these forest fragments.
Strategy for Migrating Legacy Applications to Cloud (SoMLAC)

Any modern business utilizes a number of IT-solutions for its day to day functions, for example accounting, resource planning and human resource management. This often requires large investment along with high maintenance costs, even after this these systems become obsolete and require to be updated with further capital investment. This also forces businesses to focus on solving problems which are not related to their core business areas. It is because of these problems that businesses wish to move away from managing large data centers of their own and to migrate these legacy applications and operations to the cloud. The few migration methods which exist are insufficient to be used for migration of legacy systems to the cloud infrastructure. There is a lack of research proposals in this field which focus on the problems which an organization encounters and needs to resolve while migrating legacy application to the cloud. Some of these factors are (1) Data segregation and security in a multitenant environment, (2) Application availability, (3) Application as well as data portability within cloud, (4) Effectiveness of different architectures (functionality and cost). The goal of this thesis is to develop a cloud migration strategy which shall help an organization to systematically identify the changes which the legacy application requires in its architecture and design before it can be migrated from existing in house IT infrastructure to the cloud. It is to help organizations in planning, decision making and migration of their legacy applications to the cloud. The thesis presents a migration strategy called Strategy for Migrating Legacy Applications to Cloud, SoMLAC. Research made to develop this migration strategy is qualitative and consisted of the development of a preliminary strategy based on interviews, literature study and system observations. The preliminary strategy was later refined with the help of interviews and action research. The final SoMLAC strategy consists of three migration phases where during the first phase organization migrates its legacy application to the cloud infrastructure, while in the second phase the strategy helps the organization to develop a platform for migration other legacy applications. The third and final phase helps an organization to transform these legacy applications so as to become services which can be used by other organizations. SoMLAC also contains SoMLAC compliance checklist which helps an organization during initial planning and decision making process. The checklist can also be used to validate if a cloud application meets the obligations that an organization has towards maintenance of its customer information.
The Child and Newborn

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children. The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0,. 4%. Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%. For chronically infected patients, treatment with recombinant polyethylene glycol (PEG)interferon α-2b and daily rebavirin has now been approved as standard treatment for children 2-17 years of age. In five large prospective studies, a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEGinterferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15mg/kg per day) or PEGinterferon α-2a with ribavirin. Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with tenotype 2 and 3 mainly for 24 wk. Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients. Stratified for genotype; 120/234 (51%) with genotype 1, 68/73 (93%) with genotype 2/3, and 6/11 (55%) with genotype 4 showed SVR. Relapse rate was between 7.7% and 17%. Overall, treatment was well tolerated; however, notable side effects were present in approximately 20%. According to recent experiences in the treatment of chronic hepatitis C in children and adolescents, a combination of PEG-interferon a with ribavirin has been found to be well tolerated and highly efficacious, particularly in individuals with genotype 2/3. Thus, this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.
SVC Placement for ATC Enhancement using WIPSO Technique

Available transfer Capacity (ATC) is an important issue for accommodating further transaction over and above already existing commitments. Determination and enhancement of ATC are important factor in deregulated operation of power systems. ATC enhancement with optimal FACTS devices can plays an important role in an efficient and secure operation of competitive markets. This paper presents a PSO algorithm based optimization technique is used for optimal placement of SVC’S for enhancing the transfer capacity of the transmission lines. The problem is solved by taking into account the variations in wheeling transactions across any two selected buses and the algorithm is used for enhancing the ATC under various load conditions in an emission economic dispatch environment and the results are compared against those obtained using WIPSO technique. The effectiveness of the proposed algorithm is demonstrated on IEEE 14, 30 and 57 bus test systems.