Miracle-dz/UniFAR-FTUs huggingface dataset:
JHU-2545 Selectively Shields Salivary Glands and Kidneys during PSMA-Targeted Radiotherapy

PURPOSE Prostate-specific membrane antigen (PSMA) radiotherapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) with several beta or alpha particle-emitting radionuclide-conjugated small molecules showing efficacy in late stage patients. However, PSMA is also expressed in kidneys and salivary glands where specific uptake causes dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2- (phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Selective delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radiotherapy. EXPERIMENTAL DESIGN A tri-alkoxycarbonyloxy alkyl (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Preclinical pharmacokinetic and imaging experiments were conducted prior to assessment in 3 mCRPC patients receiving PSMA PET and radiotherapy. RESULTS JHU-2545 resulted in 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers 68Ga-PSMA-11 and 18F-DCFPyL by up to 85% without effect on tumor. In a mCRPC patient, JHU-2545 treatment prior to 68Ga-PSMA-617 administration reduced kidney SUVmax by 76% without effect on metastatic lesions. When administered prior to injection of the beta emitter 177Lu-PSMA-617, JHU-2545 shielded both the salivary glands (72% Gy reduction) and kidneys (45% Gy reduction) without effect on metastases’ dose. CONCLUSIONS JHU-2545 pre-treatment raises the cumulative dose limit and improves the safety and efficacy profile of PSMA radiotherapy. STATEMENT OF TRANSLATIONAL RELEVANCE Prostate Specific Membrane Antigen (PSMA) molecular radiotherapy has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC), but endogenous expression of PSMA in kidneys and salivary glands causes uptake into these organs resulting in dose-limiting toxicities. We describe the discovery of JHU-2545, a PSMA inhibitor prodrug that selectively blocks kidney and salivary gland uptake of PSMA theranostics without altering tumor uptake in both preclinical models and in mCRPC patients. Pretreatment of JHU-2545 thereby improves the safety and efficacy profile of the multiple PSMA radiotherapies in development.
Milk Production in Goats on Veld Hay Supplemented with Selected Legume Forages

This study was designed to investigate the effects of supplementing silverleaf (Desmodium uncunatum), velvet bean (Mucuna pruriens) and cowpea (Vigna unguiculata) forage legumes to low quality veld hay on milk production in indigenous goats. Sixteen Mashona indigenous lactating goats (weighing 30±2 kg) in their third parity were divided into four dietary treatment groups and used in a completely randomized design experiment. The daily feed intake on the treatment diets and hay was significantly (P 0.05) different among the dietary groups. Milk yield was significantly different among the legume supplemented diets. Daily BW loss was significantly higher in goats supplemented with cowpea, as compared to those supplemented with commercial concentrate feed, silverleaf and velvet bean. The levels of milk production attained in this study implied that commercial concentrate feeds can be substituted with forage legumes without affecting either the milk yield or composition in goats and at lower cost especially for resourceconstrained farming areas.
Does female with chromosome translocation have a normal response to controlled ovarian hyperstimulation?

Patients with chromosomal translocation have been reported to have high risk of reproductive failure, lower ovarian response, recurrent pregnancy loss and implantation failure. The literature is not conclusive, and our objective is to study if female balanced translocation (BT) does affect the controlled ovarian stimulation (COS). We carried out a retrospective analysis of 3249 karyotypes between 2008 and 2016, including 2276 females and 973 males. 12 women (0.5%) with BT were compared with 93 control normal karyotype group (CN) in both female and male partner. An equivalent control group (EQc) of 12 patients was additionally selected to be accurate with the BT statistical contrast. Cycle, oocyte and embryo outcomes were analysed. We concluded that female BT carriers have no diminished response to COS than infertile females with normal karyotype. This is an important information for counselling couples previous to COS and preimplantational genetic testing (PGT).
How Far Does Highly Active Antiretroviral Treatment Reduce TB Incidence among Children? A Marginal Structural Modeling Analysis, Southwest Ethiopia

Background Children younger than 15 years, carry almost 80% of the global burden of HIV/AIDS. HIV worsens the progression of latent TB to active TB disease. Although antiretroviral treatment has shown marked reduction in Tuberculosis incidence, TB continues to occur in Sub-Saharan countries including Ethiopia. The aim of this study was to investigate the impact of HAART on the incidence of tuberculosis among children infected with HIV in Southwest Ethiopia. Methods A retrospective cohort study was conducted between 2009 to 2014. We used chi-square test, and Mann-Whitney U test to compare non-HAART and HAART cohort. We estimated the effect of HAART on TB incidence using marginal structural model after adjusting for time-dependent confounders affected by exposure. Result A total of 844 children were followed. We observed them for a median of 51 months (IQR 31) and a total of 2942.99 child-years. The overall TB incidence rate was 7.917 per 100 child years (95% CI, 6.933–9.002). TB incidence for specific HAART and non-HAART cohort were 7.67 per 100 child-years (95% CI, 6.318–9.217) and 8.17 per 100 child-years (95% CI, 6.772–9.767) respectively. From marginal structural modeling, children on HAART were 36% (HR=0.642, 95% CI 0.442–0.931, p<0.02) less likely to develop TB compared to those who were not. Conclusion HAART reduced the hazard of TB in HIV-infected children by 36%. This is by far less than what is expected.
Effects of tropical storms on the demography of reef corals

Disturbances, such as cyclones, have a major effect on the structure and dynamics of coral reef assemblages. However, the effect of cyclones on demographic traits, such as fecundity, has rarely been quantified, and direct estimates of mortality at the species level are rare. Here, we document the effect of Severe Tropical Cyclone Nathan on the demography of corals on the reef crest at Trimodal Reef in the northern Great Barrier Reef. Mortality rates based on tagged colonies were very high, ranging from 85.2% in Goniastrea retiformis to 100% in 6 Acropora species, 3 to 40 times higher than averages rates in the 5 yr preceding Cyclone Nathan. Fecundity was lower in 3 out of the 4 species examined following the cyclone, and egg carbon content was reduced by 58-63% in the 2 species examined. These results suggest that energy normally invested in reproduction was diverted to other processes such as injury repair and demonstrate that cyclones have important sub-lethal effects in addition to high rates of whole colony mortality. Coral cover was reduced from 34.9 ± 3.9% (mean ± SE) to 3.4 ± 1.5%, with reductions in the cover of all taxa except those with predominantly massive morphologies such as the Poritidae. A projected increase in the frequency of tropical storms as a result of global warming, combined with an increase in the frequency and scale of coral bleaching, suggest a fundamental shift in mortality regimes on reefs which has the potential to threaten their long-term persistence.
First-Principles Studies of Structural Domain Walls

This chapter discusses representative first-principles studies of structural domain walls in ferroics, focusing on the compounds that have received most attention by the simulations community so far: perovskite oxides. It describes in some detail a reduced number of case studies that come handy to illustrate different effects and to highlight the added value of the first-principles investigations. As regards the simulation methods, the chapter focuses on applications of density functional theory (DFT), typically employing an approximation for an effective treatment of ionic cores. A discussion on the application to domain-wall problems of first-principles-based methods for large-scale simulations of ferroelectrics and ferroelastics is also included. Finally, this chapter briefly on the opportunities and challenges for first-principles research in this field.
Rodent species composition, relative abundance, and habitat association in the Mabira Central Forest Reserve, Uganda

Abstract. A study was conducted in Mabira Central Forest Reserve in Uganda to determine rodent species composition, relative abundance, and habitat association. A total of 1,030 rodents belonging to 14 species were captured on 10,584 trap nights. Rodent species recorded include: Lophuromys stanleyi, Hylomyscus stella, Praomys jacksoni, Mastomys natalensis, Lophuromys ansorgei, Lemniscomys striatus, Aethomys hindei, Mus triton, Mus minutoides, Deomys ferrugineus, Gerbilliscus kempi, Rattus rattus, Grammomys kuru, and Hybomys univittatus. Overall, L. stanleyi (23.7%) was the most dominant species followed by H. stella, P. jacksoni, and M. natalensis. Species richness and evenness was highest in the regenerating forest habitat and least in the intact forest habitat. Rodent abundance was significantly affected by habitat type. The regenerating forest habitat had the highest number of animals, while the lowest numbers were observed in the depleted forest habitat. Species diversity was higher in regenerating forest habitat and lowest in the intact forest. The three habitats appeared distinct in terms of rodent species composition and there was a strong association between the two trapping grids in the same habitat type. All ordination plots showed that different rodent species consistently associated with distinct habitats. Habitat type and seasonal changes influenced rodent composition, relative abundance and habitat association. Composition of rodent community reflected the level of habitat degradation and can be used as a proxy for evaluating the biodiversity of lowland tropical forests.
CUSTOMER LOYALTY AS MEDIATOR ON THE RELATIONSHIPT BETWEEN SOCIAL MEDIA INFLUENCER AND PURCHASE INTENTION: A PROPOSED FRAMEWORK

Customer loyalty has drawn significant interest among marketing practitioners and marketing literature for over decades. A number of arguments and empirical supports have revealed existing relationship between social media influencer and customer loyalty, social media influencer and purchase intention and customer loyalty and purchase intention. These existing relationships among the variables suggested customer loyalty as a possible mediator on the relationship between social media influencer and purchase intention. Hence, this paper proposes a framework that presents customer loyalty as an intervening factor in the link between social media influencer and purchase intention. This model has provided the needed arguments and empirical supports for which future studies can be based.
Role of potassium and arbuscular mycorrhizal fungi in alleviation of water stress on Vigna mungo

A pot culture experiment was carried out under greenhouse conditions to study the effect of potassium fertilizer (70 mg kg–1, K1, and 100 mg kg–1, K2) and arbuscular mycorrhizal fungi (Glomus mosseae and Acaulospora laevis) alone and in different combinations on water stress amelioration of Vigna mungo during three growth stages. Treatment of the plants with mycorrhizal fungi and potassium improved physiological parameters including chlorophyll concentration, membrane stability, phosphatase activity, leaf protein concentration and mycorrhization over the untreated control regardless of water stress treatments. Imposition of water stress at reproductive stage caused maximum reduction in membrane stability, leaf protein concentration, phosphatase activity and mycorrhization as compared to stress during other stages. Treatment combinations of G. mosseae + A. laevis + K2 and G. mosseae + A. laevis + K1 proved to be the best for promoting physiological and morphological parameters studied both in stressed and unstressed plants. A combination of G. mosseae and K2 was the best among double inoculation treatments while G. mosseae was the best among single treatments of either dose of potassium and A. laevis for stress alleviation and growth amelioration. Imposition of water stress during vegetative stage had the least effect on the physiological parameters studied, except for leaf area, which was adversely affected. Chlorophyll concentration was the most affected parameter by water stress at the pod formation stage.
Contribution to the knowledge on relic Stipa spp.-dominated ultramafic grasslands of the Central Balkans

Abstract The heterogeneity of the ultramafic vegetation of the Central Balkans is rather great. Although this vegetation has been continuously investigated, some gaps are still to be filled. For example, the lack of available data on ultramafic vegetation of the Republic of Macedonia is evident. In that light, we have investigated different relic Stipa species-dominated dry grasslands over ultramafic bedrock. Twenty relevés were made and compared to the similar vegetation types (i.e. Potentilla visianii, Centaureo kosaninii-Bromion fibrosi, “Thymion jankae”, Saturejo-Thymion and Alyssion heldreichii) by means of numerical analyses. We distinguished one new association and one informal community, providing them with diagnosis and lists of diagnostic, constant and dominant species. We also determined their syntaxonomic positions and relations to ultramafic syntaxa from the neighboring countries.
Tumour Expression of Histone Deacetylases in Uveal Melanoma

Purpose: To determine the expression of histone deacetylase enzymes in uveal melanoma tumour cells. Procedures: This is an observational immunohistochemical study of 16 formalin-fixed, paraffin-embedded eyes enucleated for uveal melanoma between January 2001 and March 2002. Haematoxylin and eosin paraffin sections were reviewed for histopathological parameters according to the American Joint Committee on Cancer 7th edition. Sections were then immunohistochemically stained for histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2 using an automated Leica Bond II platform and Fast Red chromogen, then digitally scanned using Aperio software before assessment of staining. Results: Nuclear expression of histone deacetylases 1, 2, 3, 4 and 6 and of sirtuin 2 was confirmed in uveal melanoma tumour cells. In addition, the tumour cells showed cytoplasmic expression of histone deacetylases 4 and 6 and sirtuin 2. Nuclear and cytoplasmic immunostaining was also seen in intraocular tissues uninvolved by the tumour. Conclusion: Uveal melanoma tumour cells express histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2, confirming potential tissue targets for histone deacetylase inhibitors.
ACÛMULO DE NUTRIENTES NA PARTE AÉREA DO MILHO CV. P30K75 EM FUNÇÃO DA APLICAÇÃO DE FONTES DE ZINCO VIA SEMENTE

The zinc application (Zn) in seeds affects the nutrition of seedlings. This study evaluates the effect of rates of Zn applied in maize seed cv. P30K75, on the accumulation of macronutrients and micronutrients in the initial growth phase. The experiment was set in a greenhouse, through a completely randomized design, testing five rates of Zn (0; 5; 10; 20 and 40 g.kg -1 of seeds) and two sources (zinc sulphate, 22% of Zn and zinc oxide, 50% of Zn), with three replications in Jaboticabal, State of Sao Paulo, Brazil. The use of Zn sulphate promoted higher accumulation of N, K, Ca, Mg, S, B, Cu, Fe and Mn in the shoots and of N, K, Ca, Mg, S, Cu and Fe in the roots, but lowered the accumulation of B and Fe in the roots. The use of Zn oxide promoted higher accumulation of B, Cu, Fe and Mn in the shoots and of K, Mg, S and Cu in the roots but lowered the accumulation of N, Ca, B, Fe and Mn in the roots.
Previous alpine grazing experience of cows has little medium-term effect on feeding behaviour, milk yield and composition in a traditional alpine system

Abstract Previous grazing experience on high alpine pastures may help cows to optimise feed selection and minimise impairments in milk production. Eight inexperienced and eight experienced Aosta Red Pied cows were compared (primiparous:multiparous = 1:1). Measurements were performed when cows grazed sites at 600, 1800 and 2100 m a.s. l. The statistical model included experience, parity and site as fixed effects. The longest ingestion time was recorded for primiparous inexperienced cows at 1800 m a.s. l. Milk yield remained unaffected by experience, but the main milking time was shorter in inexperienced cows in the lowlands. Milk of inexperienced cows had a higher urea content than experienced cows. Somatic cell score remained unaffected by experience, but inexperienced cows had more incidences of clinical mastitis on alpine pastures. Compared with experienced cows, proportions of the fatty acids ΣC16:1 and ΣC17:1 in milk fat of inexperienced cows were higher and proportions of C18:1 t9 and C18:1 t6–8 lower. Overall, alpine grazing had substantial effects on milk yield and composition coinciding with results from previous studies. There were interactions between experience and site in milking characteristics and milk composition, and for the latter also between experience and parity. In conclusion, experience had effects on several of the variables tested, effects which were sometimes exhibited already on lowland pasture. Still, the effects of experience were much lower than those of the transhumance system. Highlights The advantages of previous site-specific and age experience of cows were studied on alpine pasture. Lack of experience had mostly minor effects on economically relevant traits. Experience helped to maintain udder health in this alpine environment.
Physicochemical and microbiological quality of honeys produced by stingless bees Scaptotrigona polysticta, Melipona illota and Tetragonisca angustula (Apidae: Meliponini) in San Martín, Peru

The honeys from stingless bees (Hymenoptera: Apidae: Meliponini) are recognized for their medicinal properties. They are commonly used by many indigenous groups around the world. However, in Peru stingless beekeeping is practiced in an artisanal way and the honeys remain products whose qualities are still little studied. The objective of this work was to analyze physicochemical characteristics and microbiological quality of honeys produced by Scaptotrigona polysticta Moure, Melipona illota Cockerell and Tetragonisca angustula Latreille in apiaries of department of San Martin, Peru. In June and November 2019, 30 honey samples were collected from 24 colonies housed in two apiaries in the towns of Tarapoto and Chasuta. Significant differences (p 10 CFU / mL) according Peruvian sanitary norm № 071-Minsa/Digesa-V.01, in 30 and 50% of the samples of S. polysticta and T. angustula, respectively. These results contribute to the knowledge of the stingless bee honeys of Peru providing important references for the quality standard setting process and the advancement of stingless beekeeping.
The Mediation Effect of Innovative Behavior on the Relationship Between Entrepreneurial Self-Efficacy and Entrepreneurial Intention

Purpose: This paper analyzes the mediating effect of innovative behavior on the relationship between entrepreneurial self-efficacy and entrepreneurial intention. Design/Methodology/Approach: Partial least squares structural equation modeling (PLS-SEM) was used in a sample of 358 owners in medium and big companies in a textile cluster in Peru. Findings: Results show that there is a significant complementary mediation effect of innovative behavior between entrepreneurial self-efficacy and entrepreneurial intention. Practical Implications: This finding is important in order to further advance the understanding of the direct and indirect causes of entrepreneurial intention. Originality/Value: Finally, this is especially important for understanding entrepreneurial intention in an extractive emerging economy.
Enteric Nervous System Remodeling in a Rat Model of Spinal Cord Injury: A Pilot Study

The physiopathology of digestive disorders in patients with spinal cord injury (SCI) remains largely unknown, particularly the involvement of the enteric nervous system (ENS). We aimed in a rat model of chronic thoracic SCI to characterize (1) changes in the neurochemical coding of enteric neurons and their putative consequences upon neuromuscular response, and (2) the inflammatory response of the colon. Ex vivo motility of proximal and distal colon segments of SCI and control (CT) rats were studied in an organ chamber in response to electrical field stimulation (EFS) and bethanechol. Immunohistochemical analysis of proximal and distal segments was performed using antibodies again Hu, neuronal nitric oxide synthase, (nNOS), and choline acetyltransferase. Colonic content of acetylcholine and acetylcholinesterase was measured; messenger RNA (mRNA) expression of inflammatory cytokines was measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) approaches. Compared with the CT rats, the contractile response to bethanechol was significantly decreased in the proximal colon of SCI rats but not in the distal colon. The proportion of nNOS immunoreactive (IR) neurons was significantly reduced in the proximal but not distal colon of SCI rats. No change in proportion of choline acetyltransferase (ChAT)-IR was reported; the tissue concentration of acetylcholine was significantly decreased in the proximal colon of SCI rats. The expression of tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) was significantly reduced in the proximal and distal colon of SCI rats. This study demonstrates that functional motor and enteric neuroplastic changes affect preferentially the proximal colon compared with the distal colon. The underlying mechanisms and factors responsible for these changes remain to be discovered.
Believe Me: The Evangelical Road to Donald Trump.

The ability to synthesize is a necessity for research in the field of social studies. In this sense, the author John Fea shows such capacity in his work: Believe Me: The Evangelical Road to Donald Trump, in addition to showing great ability to connect issues consistently. The general description refers to the state of mind of citizenship regarding religious feelings and beliefs. It is a very interesting question, since it raises several thematic approaches that do not usually have resonance in journalistic analysis at the present moment.